Büttner lab


Tosal-Castano S, Peselj C, Kohler V, Habernig L, Berglund LL, Ebrahimi M, Vögtle FN, Höög J, Andréasson C, Büttner S.
Snd3 controls nucleus-vacuole junctions in response to glucose signaling.
Cell Rep. 2021
Membrane contact sites facilitate the exchange of metabolites between organelles to support interorganellar communication. The nucleus-vacuole junctions (NVJs) establish physical contact between the perinuclear endoplasmic reticulum (ER) and the vacuole. Although the NVJ tethers are known, how NVJ abundance and composition are controlled in response to metabolic cues remains elusive. Here, we identify the ER protein Snd3 as central factor for NVJ formation. Snd3 interacts with NVJ tethers, supports their targeting to the contacts, and is essential for NVJ formation. Upon glucose exhaustion, Snd3 relocalizes from the ER to NVJs and promotes contact expansion regulated by central glucose signaling pathways. Glucose replenishment induces the rapid dissociation of Snd3 from the NVJs, preceding the slow disassembly of the junctions. In sum, this study identifies a key factor required for formation and regulation of NVJs and provides a paradigm for metabolic control of membrane contact sites.
Braun R, Büttner S.
Editorial: Modeling Neurodegeneration in Yeast.
Front Mol Neurosci. 2021
Most age-associated neurodegenerative disorders, including Alzheimer's, Parkinson's, Huntington's, and motoneuron disorders, are characterized by mislocalization, misfolding, and aggregation of disease-specific proteins in distinct neuronal cell populations and are therefore classified as proteopathies (Klaips et al., 2018). While diverse and partially redundant quality control mechanisms are in place to sustain proteostasis and cellular function, the accumulation of aggregation-prone proteins poses a constant burden on the proteostasis systems. With progressing cellular age, different quality control systems functionally decline, and long-lived cells such as neurons are particularly sensitive to misfolding and aggregation of proteotoxic proteins. Disease-associated oligomers and aggregates are directed to distinct protein quality control compartments, thereby compromising overall cellular fitness and survival. Proteopathies are commonly affected by disturbances of protein quality control subroutines, but also by impaired vesicle trafficking and critical mitochondrial damage. For dissecting pivotal interactions among different cellular pathways in the context of proteotoxicity, various cellular models have been established, including the baker's yeast Saccharomyces cerevisiae (Braun et al., 2010). S. cerevisiae is a genetically amenable unicellular eukaryotic model organism with a high degree of evolutionary conservation, in particular in respect to fundamental cellular processes such as protein quality control pathways, mitochondrial function and vesicle transport. Humanized yeast models based on the expression of human disease-associated aggregation-prone proteins have been successfully used to delineate molecular pathways underlying the loss of cellular fitness. In the Research Topic "Modeling Neurodegeneration in Yeast," we invited researchers to critically summarize recent developments and to present novel data using yeast to study human proteopathies.
Klionsky DJ et al.
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).
Autophagy. 2021
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Berndtsson J, Aufschnaiter A, Rathore S, Marin-Buera L, Dawitz H, Diessl J, Kohler V, Barrientos A, Büttner S, Fontanesi F, Ott M.
Respiratory supercomplexes enhance electron transport by decreasing cytochrome c diffusion distance.
EMBO Rep. 2020
Respiratory chains are crucial for cellular energy conversion and consist of multi-subunit complexes that can assemble into supercomplexes. These structures have been intensively characterized in various organisms, but their physiological roles remain unclear. Here, we elucidate their function by leveraging a high-resolution structural model of yeast respiratory supercomplexes that allowed us to inhibit supercomplex formation by mutation of key residues in the interaction interface. Analyses of a mutant defective in supercomplex formation, which still contains fully functional individual complexes, show that the lack of supercomplex assembly delays the diffusion of cytochrome c between the separated complexes, thus reducing electron transfer efficiency. Consequently, competitive cellular fitness is severely reduced in the absence of supercomplex formation and can be restored by overexpression of cytochrome c. In sum, our results establish how respiratory supercomplexes increase the efficiency of cellular energy conversion, thereby providing an evolutionary advantage for aerobic organisms.
Cavinato M, Madreiter-Sokolowski CT, Büttner S, Schosserer M, Zwerschke W, Wedel S, Grillari J, Graier WF, Jansen-Dürr P.
Targeting cellular senescence based on inter-organelle communication, multi-level proteostasis and metabolic control.
FEBS J. 2020
Cellular senescence, a stable cell division arrest caused by severe damage and stress, is a hallmark of aging in vertebrates including humans. With progressing age, senescent cells accumulate in a variety of mammalian tissues, where they contribute to tissue aging, identifying cellular senescence as a major target to delay or prevent aging. There is an increasing demand for the discovery of new classes of small molecules which would either avoid or postpone cellular senescence by selectively eliminating senescent cells from the body (i.e. "senolytics") or inactivating/switching damage-inducing properties of senescent cells (i.e. "senostatics/senomorphics"), such as the senescence-associated secretory phenotype. Whereas compounds with senolytic or senostatic activity have already been described, their efficacy and specificity has not been fully established for clinical use yet. Here, we review mechanisms of senescence that are related to mitochondria and their inter-organelle communication, and the involvement of proteostasis networks and metabolic control in the senescent phenotype. These cellular functions are associated with cellular senescence in in vitro and in vivo models but have not been fully exploited for the search of new compounds to counteract senescence yet. Therefore, we explore possibilities to target these mechanisms as new opportunities to selectively eliminate and/or disable senescent cells with the aim of tissue rejuvenation. We assume that this research will provide new compounds from the chemical space which act as mimetics of caloric restriction, modulators of calcium signaling and mitochondrial physiology, or as proteostasis optimizers, bearing the potential to counteract cellular senescence, thereby allowing healthy aging.
Toth A, Aufschnaiter A, Fedotovskaya O, Dawitz H, Ädelroth P, Büttner S, Ott M.
Membrane-tethering of cytochrome c accelerates regulated cell death in yeast.
Cell Death Dis. 2020
Intrinsic apoptosis as a modality of regulated cell death is intimately linked to permeabilization of the outer mitochondrial membrane and subsequent release of the protein cytochrome c into the cytosol, where it can participate in caspase activation via apoptosome formation. Interestingly, cytochrome c release is an ancient feature of regulated cell death even in unicellular eukaryotes that do not contain an apoptosome. Therefore, it was speculated that cytochrome c release might have an additional, more fundamental role for cell death signalling, because its absence from mitochondria disrupts oxidative phosphorylation. Here, we permanently anchored cytochrome c with a transmembrane segment to the inner mitochondrial membrane of the yeast Saccharomyces cerevisiae, thereby inhibiting its release from mitochondria during regulated cell death. This cytochrome c retains respiratory growth and correct assembly of mitochondrial respiratory chain supercomplexes. However, membrane anchoring leads to a sensitisation to acetic acid-induced cell death and increased oxidative stress, a compensatory elevation of cellular oxygen-consumption in aged cells and a decreased chronological lifespan. We therefore conclude that loss of cytochrome c from mitochondria during regulated cell death and the subsequent disruption of oxidative phosphorylation is not required for efficient execution of cell death in yeast, and that mobility of cytochrome c within the mitochondrial intermembrane space confers a fitness advantage that overcomes a potential role in regulated cell death signalling in the absence of an apoptosome.
Duan J, Zhao Y, Li H, Habernig L, Gordon MD, Miao X, Engström Y, Büttner S.
Bab2 Functions as an Ecdysone-Responsive Transcriptional Repressor during Drosophila Development.
Cell Rep. 2020
Drosophila development is governed by distinct ecdysone steroid pulses that initiate spatially and temporally defined gene expression programs. The translation of these signals into tissue-specific responses is crucial for metamorphosis, but the mechanisms that confer specificity to systemic ecdysone pulses are far from understood. Here, we identify Bric-à-brac 2 (Bab2) as an ecdysone-responsive transcriptional repressor that controls temporal gene expression during larval to pupal transition. Bab2 is necessary to terminate Salivary gland secretion (Sgs) gene expression, while premature Bab2 expression blocks Sgs genes and causes precocious salivary gland histolysis. The timely expression of bab2 is controlled by the ecdysone-responsive transcription factor Broad, and manipulation of EcR/USP/Broad signaling induces inappropriate Bab2 expression and termination of Sgs gene expression. Bab2 directly binds to Sgs loci in vitro and represses all Sgs genes in vivo. Our work characterizes Bab2 as a temporal regulator of somatic gene expression in response to systemic ecdysone signaling.
Kohler V, Aufschnaiter A, Büttner S.
Closing the Gap: Membrane Contact Sites in the Regulation of Autophagy.
Cells. 2020
In all eukaryotic cells, intracellular organization and spatial separation of incompatible biochemical processes is established by individual cellular subcompartments in form of membrane-bound organelles. Virtually all of these organelles are physically connected via membrane contact sites (MCS), allowing interorganellar communication and a functional integration of cellular processes. These MCS coordinate the exchange of diverse metabolites and serve as hubs for lipid synthesis and trafficking. While this of course indirectly impacts on a plethora of biological functions, including autophagy, accumulating evidence shows that MCS can also directly regulate autophagic processes. Here, we focus on the nexus between interorganellar contacts and autophagy in yeast and mammalian cells, highlighting similarities and differences. We discuss MCS connecting the ER to mitochondria or the plasma membrane, crucial for early steps of both selective and non-selective autophagy, the yeast-specific nuclear-vacuolar tethering system and its role in microautophagy, the emerging function of distinct autophagy-related proteins in organellar tethering as well as novel MCS transiently emanating from the growing phagophore and mature autophagosome.
Diessl J, Nandy A, Schug C, Habernig L, Büttner S.
Stable and destabilized GFP reporters to monitor calcineurin activity in Saccharomyces cerevisiae.
Microb Cell. 2020
The protein phosphatase calcineurin is activated in response to rising intracellular Ca2+ levels and impacts fundamental cellular processes in organisms ranging from yeast to humans. In fungi, calcineurin orchestrates cellular adaptation to diverse environmental challenges and is essential for virulence of pathogenic species. To enable rapid and large-scale assessment of calcineurin activity in living, unperturbed yeast cells, we have generated stable and destabilized GFP transcriptional reporters under the control of a calcineurin-dependent response element (CDRE). Using the reporters, we show that the rapid dynamics of calcineurin activation and deactivation can be followed by flow cytometry and fluorescence microscopy. This system is compatible with live/dead staining that excludes confounding dead cells from the analysis. The reporters provide technology to monitor calcineurin dynamics during stress and ageing and may serve as a drug-screening platform to identify novel antifungal compounds that selectively target calcineurin.
Aufschnaiter A, Kohler V, Büttner S.
Chapter 8 - The mitochondrial network in Parkinson's disease
Genetics, Neurology, Behavior, and Diet in Parkinson's Disease,
Academic Press, 2020
Neuronal dysfunction during sporadic and familial forms of Parkinson's disease is intimately connected to mitochondrial dysfunction. Diverse genetic and environmental factors contributing to Parkinson's disease development and progression have been shown to interfere with and to compromise mitochondrial bioenergetics, dynamics and trafficking. Mitochondria are highly dynamic organelles, constantly changing shape and abundance via coordinated fission and fusion events to adapt to cellular needs. Moreover, direct contact between mitochondria and other organelles allows interconnected signaling, and exchange of metabolites and ions. Several proteins associated with familial Parkinson's disease modulate the equilibrium between fission and fusion, govern distinct mitochondrial degradation pathways and impact the formation of tethering complexes that facilitate interorganellar contact. Here, we discuss molecular mechanisms of mitochondrial dysfunction in Parkinson's disease, focusing on mitochondrial dynamics and contact sites.
Aufschnaiter A, Kohler V, Khalifa S, Abd El-Wahed A, Du M, El-Seedi H, Büttner S.
Apitoxin and Its Components against Cancer, Neurodegeneration and Rheumatoid Arthritis: Limitations and Possibilities.
Toxins. 2020
Natural products represent important sources for the discovery and design of novel drugs. Bee venom and its isolated components have been intensively studied with respect to their potential to counteract or ameliorate diverse human diseases. Despite extensive research and significant advances in recent years, multifactorial diseases such as cancer, rheumatoid arthritis and neurodegenerative diseases remain major healthcare issues at present. Although pure bee venom, apitoxin, is mostly described to mediate anti-inflammatory, anti-arthritic and neuroprotective effects, its primary component melittin may represent an anticancer therapeutic. In this review, we approach the possibilities and limitations of apitoxin and its components in the treatment of these multifactorial diseases. We further discuss the observed unspecific cytotoxicity of melittin that strongly restricts its therapeutic use and review interesting possibilities of a beneficial use by selectively targeting melittin to cancer cells.
Charmpilas N, Ruckenstuhl C, Sica V, Büttner S, Habernig L, Dichtinger S, Madeo F, Tavernarakis N, Bravo-San Pedro JM, Kroemer G.
Acyl-CoA-binding protein (ACBP): a phylogenetically conserved appetite stimulator.
Cell Death Dis. 2020
Recently, we reported that, in mice, hunger causes the autophagy-dependent release of a protein called "acyl-CoA-binding protein" or "diazepam binding inhibitor" (ACBP/DBI) from cells, resulting in an increase in plasma ACBP concentrations. Administration of extra ACBP is orexigenic and obesogenic, while its neutralization is anorexigenic in mice, suggesting that ACBP is a major stimulator of appetite and lipo-anabolism. Accordingly, obese persons have higher circulating ACBP levels than lean individuals, and anorexia nervosa is associated with subnormal ACBP plasma concentrations. Here, we investigated whether ACBP might play a phylogenetically conserved role in appetite stimulation. We found that extracellular ACBP favors sporulation in Saccharomyces cerevisiae, knowing that sporulation is a strategy for yeast to seek new food sources. Moreover, in the nematode Caenorhabditis elegans, ACBP increased the ingestion of bacteria as well as the frequency pharyngeal pumping. These observations indicate that ACBP has a phylogenetically ancient role as a 'hunger factor' that favors food intake.
Poveda-Huertes D, Matic S, Marada A, Habernig L, Licheva M, Myketin L, Gilsbach R, Tosal-Castano S, Papinski D, Mulica P, Kretz O, Kücükköse C, Taskin AA, Hein L, Kraft C, Büttner S, Meisinger C, Vögtle FN.
An Early mtUPR: Redistribution of the Nuclear Transcription Factor Rox1 to Mitochondria Protects against Intramitochondrial Proteotoxic Aggregates.
Mol Cell. 2020
The mitochondrial proteome is built mainly by import of nuclear-encoded precursors, which are targeted mostly by cleavable presequences. Presequence processing upon import is essential for proteostasis and survival, but the consequences of dysfunctional protein maturation are unknown. We find that impaired presequence processing causes accumulation of precursors inside mitochondria that form aggregates, which escape degradation and unexpectedly do not cause cell death. Instead, cells survive via activation of a mitochondrial unfolded protein response (mtUPR)-like pathway that is triggered very early after precursor accumulation. In contrast to classical stress pathways, this immediate response maintains mitochondrial protein import, membrane potential, and translation through translocation of the nuclear HMG-box transcription factor Rox1 to mitochondria. Rox1 binds mtDNA and performs a TFAM-like function pivotal for transcription and translation. Induction of early mtUPR provides a reversible stress model to mechanistically dissect the initial steps in mtUPR pathways with the stressTFAM Rox1 as the first line of defense.
Vazquez-Calvo C, Suhm T, Büttner S, Ott M.
The basic machineries for mitochondrial protein quality control.
Mitochondrion. 2020
Mitochondria play pivotal roles in cellular energy metabolism, the synthesis of essential biomolecules and the regulation of cell death and aging. The proper folding, unfolding and degradation of the many proteins active within mitochondria is surveyed by the mitochondrial quality control machineries. Here, we describe the principal components of the mitochondrial quality control system and recent developments in the elucidation of the molecular mechanisms maintaining a functional mitochondrial proteome.

Andréasson C, Ott M, Büttner S.
Mitochondria orchestrate proteostatic and metabolic stress responses.
EMBO Rep. 2019
The eukaryotic cell is morphologically and functionally organized as an interconnected network of organelles that responds to stress and aging. Organelles communicate via dedicated signal transduction pathways and the transfer of information in form of metabolites and energy levels. Recent data suggest that the communication between organellar proteostasis systems is a cornerstone of cellular stress responses in eukaryotic cells. Here, we discuss the integration of proteostasis and energy fluxes in the regulation of cellular stress and aging. We emphasize the molecular architecture of the regulatory transcriptional pathways that both sense and control metabolism and proteostasis. A special focus is placed on mechanistic insights gained from the model organism budding yeast in signaling from mitochondria to the nucleus and how this shapes cellular fitness.
Gross AS, Zimmermann A, Pendl T, Schroeder S, Schoenlechner H, Knittelfelder O, Lamplmayr L, Santiso A, Aufschnaiter A, Waltenstorfer D, Ortonobes Lara S, Stryeck S, Kast C, Ruckenstuhl C, Hofer SJ, Michelitsch B, Woelflingseder M, Müller R, Carmona-Gutierrez D, Madl T, Büttner S, Fröhlich KU, Shevchenko A, Eisenberg T.
Acetyl-CoA carboxylase 1-dependent lipogenesis promotes autophagy downstream of AMPK.
J Biol Chem. 2019
Autophagy, a membrane-dependent catabolic process, ensures survival of aging cells and depends on the cellular energetic status. Acetyl-CoA carboxylase 1 (Acc1) connects central energy metabolism to lipid biosynthesis and is rate-limiting for the de novo synthesis of lipids. However, it is unclear how de novo lipogenesis and its metabolic consequences affect autophagic activity. Here, we show that in aging yeast, autophagy levels highly depend on the activity of Acc1. Constitutively active Acc1 (acc1S/A ) or a deletion of the Acc1 negative regulator, Snf1 (yeast AMPK), shows elevated autophagy levels, which can be reversed by the Acc1 inhibitor soraphen A. Vice versa, pharmacological inhibition of Acc1 drastically reduces cell survival and results in the accumulation of Atg8-positive structures at the vacuolar membrane, suggesting late defects in the autophagic cascade. As expected, acc1S/A cells exhibit a reduction in acetate/acetyl-CoA availability along with elevated cellular lipid content. However, concomitant administration of acetate fails to fully revert the increase in autophagy exerted by acc1S/A Instead, administration of oleate, while mimicking constitutively active Acc1 in WT cells, alleviates the vacuolar fusion defects induced by Acc1 inhibition. Our results argue for a largely lipid-dependent process of autophagy regulation downstream of Acc1. We present a versatile genetic model to investigate the complex relationship between acetate metabolism, lipid homeostasis, and autophagy and propose Acc1-dependent lipogenesis as a fundamental metabolic path downstream of Snf1 to maintain autophagy and survival during cellular aging.
Aufschnaiter A, Büttner S.
The vacuolar shapes of ageing: From function to morphology.
BBA - Mol Cell Res. 2019
Cellular ageing results in accumulating damage to various macromolecules and the progressive decline of organelle function. Yeast vacuoles as well as their counterpart in higher eukaryotes, the lysosomes, emerge as central organelles in lifespan determination. These acidic organelles integrate enzymatic breakdown and recycling of cellular waste with nutrient sensing, storage, signalling and mobilization. Establishing physical contact with virtually all other organelles, vacuoles serve as hubs of cellular homeostasis. Studies in Saccharomyces cerevisiae contributed substantially to our understanding of the ageing process per se and the multifaceted roles of vacuoles/lysosomes in the maintenance of cellular fitness with progressing age. Here, we discuss the multiple roles of the vacuole during ageing, ranging from vacuolar dynamics and acidification as determinants of lifespan to the function of this organelle as waste bin, recycling facility, nutrient reservoir and integrator of nutrient signalling.

Kohler V, Goessweiner-Mohr N, Aufschnaiter A, Fercher C, Probst I, Pavkov-Keller T, Hunger K, Wolinski H, Büttner S, Grohmann E, Keller W.
TraN: A novel repressor of an Enterococcus conjugative type IV secretion system.
Nucleic Acids Res. 2018
The dissemination of multi-resistant bacteria represents an enormous burden on modern healthcare. Plasmid-borne conjugative transfer is the most prevalent mechanism, requiring a type IV secretion system that enables bacteria to spread beneficial traits, such as resistance to last-line antibiotics, among different genera. Inc18 plasmids, like the Gram-positive broad host-range plasmid pIP501, are substantially involved in propagation of vancomycin resistance from Enterococci to methicillin-resistant strains of Staphylococcus aureus. Here, we identified the small cytosolic protein TraN as a repressor of the pIP501-encoded conjugative transfer system, since deletion of traN resulted in upregulation of transfer factors, leading to highly enhanced conjugative transfer. Furthermore, we report the complex structure of TraN with DNA and define the exact sequence of its binding motif. Targeting this protein-DNA interaction might represent a novel therapeutic approach against the spreading of antibiotic resistances.
Büttner S, Ludovico P, Thevissen K.
From Regulated Cell Death to Adaptive Stress Strategies: Convergence and Divergence in Eukaryotic Cells.
Oxid Med Cell Longev. 2018
Aufschnaiter A, Kohler V, Walter C, Tosal-Castano S, Habernig L, Wolinski H, Keller W, Vögtle FN, Büttner S.
The Enzymatic Core of the Parkinson's Disease-Associated Protein LRRK2 Impairs Mitochondrial Biogenesis in Aging Yeast.
Front Mol Neurosci. 2018;
Mitochondrial dysfunction is a prominent trait of cellular decline during aging and intimately linked to neuronal degeneration during Parkinson's disease (PD). Various proteins associated with PD have been shown to differentially impact mitochondrial dynamics, quality control and function, including the leucine-rich repeat kinase 2 (LRRK2). Here, we demonstrate that high levels of the enzymatic core of human LRRK2, harboring GTPase as well as kinase activity, decreases mitochondrial mass via an impairment of mitochondrial biogenesis in aging yeast. We link mitochondrial depletion to a global downregulation of mitochondria-related gene transcripts and show that this catalytic core of LRRK2 localizes to mitochondria and selectively compromises respiratory chain complex IV formation. With progressing cellular age, this culminates in dissipation of mitochondrial transmembrane potential, decreased respiratory capacity, ATP depletion and generation of reactive oxygen species. Ultimately, the collapse of the mitochondrial network results in cell death. A point mutation in LRRK2 that increases the intrinsic GTPase activity diminishes mitochondrial impairment and consequently provides cytoprotection. In sum, we report that a downregulation of mitochondrial biogenesis rather than excessive degradation of mitochondria underlies the reduction of mitochondrial abundance induced by the enzymatic core of LRRK2 in aging yeast cells. Thus, our data provide a novel perspective for deciphering the causative mechanisms of LRRK2-associated PD pathology.
Suhm T, Kaimal JM, Dawitz H, Peselj C, Masser AE, Hanzén S, Ambrožič M, Smialowska A, Björck ML, Brzezinski P, Nyström T, Büttner S, Andréasson C, Ott M.
Mitochondrial Translation Efficiency Controls Cytoplasmic Protein Homeostasis.
Cell Metab. 2018
Cellular proteostasis is maintained via the coordinated synthesis, maintenance, and breakdown of proteins in the cytosol and organelles. While biogenesis of the mitochondrial membrane complexes that execute oxidative phosphorylation depends on cytoplasmic translation, it is unknown how translation within mitochondria impacts cytoplasmic proteostasis and nuclear gene expression. Here we have analyzed the effects of mutations in the highly conserved accuracy center of the yeast mitoribosome. Decreased accuracy of mitochondrial translation shortened chronological lifespan, impaired management of cytosolic protein aggregates, and elicited a general transcriptional stress response. In striking contrast, increased accuracy extended lifespan, improved cytosolic aggregate clearance, and suppressed a normally stress-induced, Msn2/4-dependent interorganellar proteostasis transcription program (IPTP) that regulates genes important for mitochondrial proteostasis. Collectively, the data demonstrate that cytosolic protein homeostasis and nuclear stress signaling are controlled by mitochondrial translation efficiency in an inter-connected organelle quality control network that determines cellular lifespan.
Leibiger C, Deisel J, Aufschnaiter A, Ambros S, Tereshchenko M, Verheijen BM, Büttner S, Braun RJ.
TDP-43 controls lysosomal pathways thereby determining its own clearance and cytotoxicity.
Hum Mol Genet. 2018
TDP-43 is a nuclear RNA-binding protein whose cytoplasmic accumulation is the pathological hallmark of amyotrophic lateral sclerosis (ALS). For a better understanding of this devastating disorder at the molecular level, it is important to identify cellular pathways involved in the clearance of detrimental TDP-43. Using a yeast model system, we systematically analyzed to which extent TDP-43-triggered cytotoxicity is modulated by conserved lysosomal clearance pathways. We observed that the lysosomal fusion machinery and the endolysosomal pathway, which are crucial for proper lysosomal function, were pivotal for survival of cells exposed to TDP-43. Interestingly, TDP-43 itself interfered with these critical TDP-43 clearance pathways. In contrast, autophagy played a complex role in this process. It contributed to the degradation of TDP-43 in the absence of endolysosomal pathway activity, but its induction also enhanced cell death. Thus, TDP-43 interfered with lysosomal function and its own degradation via lysosomal pathways, and triggered lethal autophagy. We propose that these effects critically contribute to cellular dysfunction in TDP-43 proteinopathies.
Yeaman MR, Büttner S, Thevissen K.
Regulated Cell Death as a Therapeutic Target for Novel Antifungal Peptides and Biologics.
Oxid Med Cell Longev. 2018
The rise of microbial pathogens refractory to conventional antibiotics represents one of the most urgent and global public health concerns for the 21st century. Emergence of Candida auris isolates and the persistence of invasive mold infections that resist existing treatment and cause severe illness has underscored the threat of drug-resistant fungal infections. To meet these growing challenges, mechanistically novel agents and strategies are needed that surpass the conventional fungistatic or fungicidal drug actions. Host defense peptides have long been misunderstood as indiscriminant membrane detergents. However, evidence gathered over the past decade clearly points to their sophisticated and selective mechanisms of action, including exploiting regulated cell death pathways of their target pathogens. Such peptides perturb transmembrane potential and mitochondrial energetics, inducing phosphatidylserine accessibility and metacaspase activation in fungi. These mechanisms are often multimodal, affording target pathogens fewer resistance options as compared to traditional small molecule drugs. Here, recent advances in the field are examined regarding regulated cell death subroutines as potential therapeutic targets for innovative anti-infective peptides against pathogenic fungi. Furthering knowledge of protective host defense peptide interactions with target pathogens is key to advancing and applying novel prophylactic and therapeutic countermeasures to fungal resistance and pathogenesis.
Leibiger C, Deisel J, Aufschnaiter A, Ambros S, Tereshchenko M, Verheijen BM, Büttner S, Braun RJ.
Endolysosomal pathway activity protects cells from neurotoxic TDP-43.
Microb Cell. 2018
The accumulation of protein aggregates in neurons is a typical pathological hallmark of the motor neuron disease amyotrophic lateral sclerosis (ALS) and of frontotemporal dementia (FTD). In many cases, these aggregates are composed of the 43 kDa TAR DNA-binding protein (TDP 43). Using a yeast model for TDP 43 proteinopathies, we observed that the vacuole (the yeast equivalent of lysosomes) markedly contributed to the degradation of TDP 43. This clearance occurred via TDP 43-containing vesicles fusing with the vacuole through the concerted action of the endosomal-vacuolar (or endolysosomal) pathway and autophagy. In line with its dominant role in the clearance of TDP 43, endosomal-vacuolar pathway activity protected cells from the detrimental effects of TDP 43. In contrast, enhanced autophagy contributed to TDP 43 cytotoxicity, despite being involved in TDP 43 degradation. TDP 43's interference with endosomal-vacuolar pathway activity may have two deleterious consequences. First, it interferes with its own degradation via this pathway, resulting in TDP 43 accumulation. Second, it affects vacuolar proteolytic activity, which requires endosomal-vacuolar trafficking. We speculate that the latter contributes to aberrant autophagy. In sum, we propose that ameliorating endolysosomal pathway activity enhances cell survival in TDP 43-associated diseases.
Rockenfeller P, Smolnig M, Diessl J, Bashir M, Schmiedhofer V, Knittelfelder O, Ring J, Franz J, Foessl I, Khan MJ, Rost R, Graier WF, Kroemer G, Zimmermann A, Carmona-Gutierrez D, Eisenberg T, Büttner S, Sigrist SJ, Kühnlein RP, Kohlwein SD, Gourlay CW, Madeo F.
Diacylglycerol triggers Rim101 pathway-dependent necrosis in yeast: a model for lipotoxicity.
Cell Death Differ. 2018
The loss of lipid homeostasis can lead to lipid overload and is associated with a variety of disease states. However, little is known as to how the disruption of lipid regulation or lipid overload affects cell survival. In this study we investigated how excess diacylglycerol (DG), a cardinal metabolite suspected to mediate lipotoxicity, compromises the survival of yeast cells. We reveal that increased DG achieved by either genetic manipulation or pharmacological administration of 1,2-dioctanoyl-sn-glycerol (DOG) triggers necrotic cell death. The toxic effects of DG are linked to glucose metabolism and require a functional Rim101 signaling cascade involving the Rim21-dependent sensing complex and the activation of a calpain-like protease. The Rim101 cascade is an established pathway that triggers a transcriptional response to alkaline or lipid stress. We propose that the Rim101 pathway senses DG-induced lipid perturbation and conducts a signaling response that either facilitates cellular adaptation or triggers lipotoxic cell death. Using established models of lipotoxicity, i.e., high-fat diet in Drosophila and palmitic acid administration in cultured human endothelial cells, we present evidence that the core mechanism underlying this calpain-dependent lipotoxic cell death pathway is phylogenetically conserved.
Suhm T, Habernig L, Rzepka M, Kaimal JM, Andréasson C, Büttner S, Ott M.
A novel system to monitor mitochondrial translation in yeast.
Microb Cell. 2018
The mitochondrial genome is responsible for the production of a handful of polypeptides that are core subunits of the membrane-bound oxidative phosphorylation system. Until now the mechanistic studies of mitochondrial protein synthesis inside cells have been conducted with inhibition of cytoplasmic protein synthesis to reduce the background of nuclear gene expression with the undesired consequence of major disturbances of cellular signaling cascades. Here we have generated a system that allows direct monitoring of mitochondrial translation in unperturbed cells. A recoded gene for superfolder GFP was inserted into the yeast (Saccharomyces cerevisiae) mitochondrial genome and enabled the detection of translation through fluorescence microscopy and flow cytometry in functional mitochondria. This novel tool allows the investigation of the function and regulation of mitochondrial translation during stress signaling, aging and mitochondrial biogenesis.
Carmona-Gutierrez D, Bauer MA, Zimmermann A, Aguilera A, Austriaco N, Ayscough K, Balzan R, Bar-Nun S, Barrientos A, Belenky P, Blondel M, Braun RJ, Breitenbach M, Burhans WC, Büttner S, Cavalieri D, et al.
Guidelines and recommendations on yeast cell death nomenclature.
Microb Cell. 2018
Elucidating the biology of yeast in its full complexity has major implications for science, medicine and industry. One of the most critical processes determining yeast life and physiology is cel-lular demise. However, the investigation of yeast cell death is a relatively young field, and a widely accepted set of concepts and terms is still missing. Here, we propose unified criteria for the defi-nition of accidental, regulated, and programmed forms of cell death in yeast based on a series of morphological and biochemical criteria. Specifically, we provide consensus guidelines on the differ-ential definition of terms including apoptosis, regulated necrosis, and autophagic cell death, as we refer to additional cell death rou-tines that are relevant for the biology of (at least some species of) yeast. As this area of investigation advances rapidly, changes and extensions to this set of recommendations will be implemented in the years to come. Nonetheless, we strongly encourage the au-thors, reviewers and editors of scientific articles to adopt these collective standards in order to establish an accurate framework for yeast cell death research and, ultimately, to accelerate the pro-gress of this vibrant field of research.

Ring J, Rockenfeller P, Abraham C, Tadic J, Poglitsch M, Schimmel K, Westermayer J, Schauer S, Achleitner B, Schimpel C, Moitzi B, Rechberger GN, Sigrist SJ, Carmona-Gutierrez D, Kroemer G, Büttner S, Eisenberg T, Madeo F.
Mitochondrial energy metabolism is required for lifespan extension by the spastic paraplegia-associated protein spartin.
Microb Cell. 2017
function mutations in the protein spartin. However, the physiological role of spartin remains largely elusive. Here we show that heterologous expression of human or Drosophila spartin extends chronological lifespan of yeast, reducing age-associated ROS production, apoptosis, and necrosis. We demonstrate that spartin localizes to the proximity of mitochondria and physically interacts with proteins related to mitochondrial and respiratory metabolism. Interestingly, Nde1, the mitochondrial external NADH dehydrogenase, and Pda1, the core enzyme of the pyruvate dehydrogenase complex, are required for spartin-mediated cytoprotection. Furthermore, spartin interacts with the glycolysis enhancer phospo-fructo-kinase-2,6 (Pfk26) and is sufficient to complement for PFK26-deficiency at least in early aging. We conclude that mitochondria-related energy metabolism is crucial for spartin's vital function during aging and uncover a network of specific interactors required for this function.
Aufschnaiter A, Kohler V, Büttner S.
Taking out the garbage: cathepsin D and calcineurin in neurodegeneration.
Neural Regen Res. 2017
Cellular homeostasis requires a tightly controlled balance between protein synthesis, folding and degradation. Especially long-lived, post-mitotic cells such as neurons depend on an efficient proteostasis system to maintain cellular health over decades. Thus, a functional decline of processes contributing to protein degradation such as autophagy and general lysosomal proteolytic capacity is connected to several age-associated neurodegenerative disorders, including Parkinson's, Alzheimer's and Huntington's diseases. These so called proteinopathies are characterized by the accumulation and misfolding of distinct proteins, subsequently driving cellular demise. We recently linked efficient lysosomal protein breakdown via the protease cathepsin D to the Ca2+/calmodulin-dependent phosphatase calcineurin. In a yeast model for Parkinson's disease, functional calcineurin was required for proper trafficking of cathepsin D to the lysosome and for recycling of its endosomal sorting receptor to allow further rounds of shuttling. Here, we discuss these findings in relation to present knowledge about the involvement of cathepsin D in proteinopathies in general and a possible connection between this protease, calcineurin signalling and endosomal sorting in particular. As dysregulation of Ca2+ homeostasis as well as lysosomal impairment is connected to a plethora of neurodegenerative disorders, this novel interplay might very well impact pathologies beyond Parkinson's disease.
Aufschnaiter A, Habernig L, Kohler V, Diessl J, Carmona-Gutierrez D, Eisenberg T, Keller W, Büttner S.
The Coordinated Action of Calcineurin and Cathepsin D Protects Against α-Synuclein Toxicity.
Front Mol Neurosci. 2017
The degeneration of dopaminergic neurons during Parkinson's disease (PD) is intimately linked to malfunction of α-synuclein (αSyn), the main component of the proteinaceous intracellular inclusions characteristic for this pathology. The cytotoxicity of αSyn has been attributed to disturbances in several biological processes conserved from yeast to humans, including Ca2+homeostasis, general lysosomal function and autophagy. However, the precise sequence of events that eventually results in cell death remains unclear. Here, we establish a connection between the major lysosomal protease cathepsin D (CatD) and the Ca2+/calmodulin-dependent phosphatase calcineurin. In a yeast model for PD, high levels of human αSyn triggered cytosolic acidification and reduced vacuolar hydrolytic capacity, finally leading to cell death. This could be counteracted by overexpression of yeast CatD (Pep4), which re-installed pH homeostasis and vacuolar proteolytic function, decreased αSyn oligomers and aggregates, and provided cytoprotection. Interestingly, these beneficial effects of Pep4 were independent of autophagy. Instead, they required functional calcineurin signaling, since deletion of calcineurin strongly reduced both the proteolytic activity of endogenous Pep4 and the cytoprotective capacity of overexpressed Pep4. Calcineurin contributed to proper endosomal targeting of Pep4 to the vacuole and the recycling of the Pep4 sorting receptor Pep1 from prevacuolar compartments back to the trans-Golgi network. Altogether, we demonstrate that stimulation of this novel calcineurin-Pep4 axis reduces αSyn cytotoxicity.
Kohler V, Probst I, Aufschnaiter A, Büttner S, Schaden L, Rechberger GN, Koraimann G, Grohmann E, Keller W.
Conjugative type IV secretion in Gram-positive pathogens: TraG, a lytic transglycosylase and endopeptidase, interacts with translocation channel protein TraM.
Plasmid. 2017
Conjugative transfer plays a major role in the transmission of antibiotic resistance in bacteria. pIP501 is a Gram-positive conjugative model plasmid with the broadest transfer host-range known so far and is frequently found in Enterococcus faecalis and Enterococcus faecium clinical isolates. The pIP501 type IV secretion system is encoded by 15 transfer genes. In this work, we focus on the VirB1-like protein TraG, a modular peptidoglycan metabolizing enzyme, and the VirB8-homolog TraM, a potential member of the translocation channel. By providing full-length traG in trans, but not with a truncated variant, we achieved full recovery of wild type transfer efficiency in the traG-knockout mutant E. faecalis pIP501ΔtraG. With peptidoglycan digestion experiments and tandem mass spectrometry we could assign lytic transglycosylase and endopeptidase activity to TraG, with the CHAP domain alone displaying endopeptidase activity. We identified a novel interaction between TraG and TraM in a bacterial-2-hybrid assay. In addition we found that both proteins localize in focal spots at the E. faecalis cell membrane using immunostaining and fluorescence microscopy. Extracellular protease digestion to evaluate protein cell surface exposure revealed that correct membrane localization of TraM requires the transmembrane helix of TraG. Thus, we suggest an essential role for TraG in the assembly of the pIP501 type IV secretion system.
Aufschnaiter A, Kohler V, Diessl J, Peselj C, Carmona-Gutierrez D, Keller W, Büttner S.
Mitochondrial lipids in neurodegeneration.
Cell Tissue Res. 2017
Mitochondrial dysfunction is a common feature of many neurodegenerative diseases, including proteinopathies such as Alzheimer's or Parkinson's disease, which are characterized by the deposition of aggregated proteins in the form of insoluble fibrils or plaques. The distinct molecular processes that eventually result in mitochondrial dysfunction during neurodegeneration are well studied but still not fully understood. However, defects in mitochondrial fission and fusion, mitophagy, oxidative phosphorylation and mitochondrial bioenergetics have been linked to cellular demise. These processes are influenced by the lipid environment within mitochondrial membranes as, besides membrane structure and curvature, recruitment and activity of different proteins also largely depend on the respective lipid composition. Hence, the interaction of neurotoxic proteins with certain lipids and the modification of lipid composition in different cell compartments, in particular mitochondria, decisively impact cell death associated with neurodegeneration. Here, we discuss the relevance of mitochondrial lipids in the pathological alterations that result in neuronal demise, focussing on proteinopathies.

≤ 2016
Eisenberg T, Abdellatif M, Schroeder S, Primessnig U, Stekovic S, Pendl T, Harger A, Schipke J, Zimmermann A, Schmidt A, Tong M, Ruckenstuhl C, Dammbrueck C, Gross AS, Herbst V, Magnes C, Trausinger G, Narath S, Meinitzer A, Hu Z, Kirsch A, Eller K, Carmona-Gutierrez D, Büttner S, Pietrocola F, Knittelfelder O, Schrepfer E, Rockenfeller P, Simonini C, Rahn A, Horsch M, Moreth K, Beckers J, Fuchs H, Gailus-Durner V, Neff F, Janik D, Rathkolb B, Rozman J, de Angelis MH, Moustafa T, Haemmerle G, Mayr M, Willeit P, von Frieling-Salewsky M, Pieske B, Scorrano L, Pieber T, Pechlaner R, Willeit J, Sigrist SJ, Linke WA, Mühlfeld C, Sadoshima J, Dengjel J, Kiechl S, Kroemer G, Sedej S, Madeo F.
Cardioprotection and lifespan extension by the natural polyamine spermidine.
Nat Med.2016
Aufschnaiter A, Büttner S.
Peroxisomal fission controls yeast life span.
Cell Cycle. 2015
Carmona-Gutierrez D, Büttner S.
The many ways to age for a single yeast cell.
Yeast. 2014
Eisenberg T, Schroeder S, Büttner S, Carmona-Gutierrez D, Pendl T, Andryushkova A, Mariño G, Pietrocola F, Harger A, Zimmermann A, Magnes C, Sinner F, Sedej S, Pieber TR, Dengjel J, Sigrist S, Kroemer G, Madeo F.
A histone point mutation that switches on autophagy.
Autophagy. 2014
Ruckenstuhl C, Netzberger C, Entfellner I, Carmona-Gutierrez D, Kickenweiz T, Stekovic S, Gleixner C, Schmid C, Klug L, Hajnal I, Sorgo AG, Eisenberg T, Büttner S, Marin O G, Koziel R, Magnes C, Sinner F, Pieber TR, Jansen-Dürr P, Fröhlich KU, Kroemer G, Madeo F.
Autophagy extends lifespan via vacuolar acidification.
Microb Cell. 2014
Ruckenstuhl C, Netzberger C, Entfellner I, Carmona-Gutierrez D, Kickenweiz T, Stekovic S, Gleixner C, Schmid C, Klug L, Sorgo AG, Eisenberg T, Büttner S, Mariño G, Koziel R, Jansen-Dürr P, Fröhlich KU, Kroemer G, Madeo F.
Lifespan extension by methionine restriction requires autophagy-dependent vacuolar acidification.
PLoS Genet. 2014
Eisenberg T, Schroeder S, Andryushkova A, Pendl T, Küttner V, Bhukel A, Mariño G, Pietrocola F, Harger A, Zimmermann A, Moustafa T, Sprenger A, Jany E, Büttner S, Carmona-Gutierrez D, Ruckenstuhl C, Ring J, Reichelt W, Schimmel K, Leeb T, Moser C, Schatz S, Kamolz LP, Magnes C, Sinner F, Sedej S, Fröhlich KU, Juhasz G, Pieber TR, Dengjel J, Sigrist SJ, Kroemer G, Madeo F.
Nucleocytosolic depletion of the energy metabolite acetyl-coenzyme a stimulates autophagy and prolongs lifespan
Cell Metab. 2014
Eisenberg T and Büttner S.
Lipids and cell death in yeast.
FEMS Yeast Res. 2013
Büttner S, Broeskamp F, Sommer C, Markaki M, Habernig L, Alavian-Ghavanini A, Carmona-Gutierrez D, Eisenberg T, Michael E, Kroemer G, Tavernarakis N, Sigrist SJ, Madeo F.
Spermidine protects against α-synuclein neurotoxicity.
Cell Cycle. 2014
Büttner S, Habernig L, Broeskamp F, Ruli D, Vögtle FN, Vlachos M, Macchi F, Küttner V, Carmona- Gutierrez D, Eisenberg T, Ring J, Markaki M, Aras Taskin A, Benke S, Ruckenstuhl C, Braun R, Van den Haute C, Bammens T, van der Perren A, Fröhlich KU, Winderickx J, Kroemer G, Baekelandt V, Tavernarakis N, Kovacs GG, Dengjel J, Meisinger C, Sigrist SJ and Madeo F.
Endonuclease G mediates α-synuclein cytotoxicity during Parkinson's disease.
EMBO J. 2013
Carmona-Gutierrez D, Alavian-Ghavanini A, Habernig L, Bauer MA, Hammer A, Rossmann C, Zimmermann AS, Ruckenstuhl C, Büttner S, Eisenberg T, Sattler W, Malle E, Madeo F.
The cell death protease Kex1p is essential for hypochlorite-induced apoptosis in yeast.
Cell Cycle. 2013
Büttner S, Faes L, Reichelt NR, Broeskamp F, Habernig L, Benke S, Kourtis N, Ruli D, D'hooge P, Ghillebert R, Eisenberg T, Carmona Gutierrez D, Franssens V, Harger A, Pieber TR, Freudenberger P, Kroemer G, Sigrist SJ, Winderickx J, Callewaert G, Tavernarkis N, Madeo F.
The Ca2+/Mn2+ ion-pump PMR1 links elevation of cytosolic Ca2+ levels to α-synuclein toxicity in Parkinson's disease models.
Cell Death Differ. 2012
Rinnerthaler M, Büttner S, Laun P, Heeren G, Felder TK, Klinger H, Weinberger M, Stolze K, Grousl T, Hasek J, Benada O, Frydlova I, Klocker A, Simon-Nobbe B, Jansko B, Breitenbach-Koller H, Eisenberg T, Gourlay CW, Madeo F, Burhans WC, Breitenbach M.
Yno1p/Aim14p, a NADPH-oxidase ortholog, controls extramitochondrial reactive oxygen species generation, apoptosis, and actin cable formation in yeast.
Proc Natl Acad Sci. 2012
Laun P, Büttner S, Rinnerthaler M, Burhans WC, Breitenbach M.
Yeast aging and apoptosis.
Subcell Biochem. 2012
Breitenbach M, Laun P, Dickinson JR, Klocker A, Rinnerthaler M, Dawes IW, Aung-Htut MT, Breitenbach-Koller L, Caballero A, Nyström T, Büttner S, Eisenberg T, Madeo F, Ralser M. The role of mitochondria in the aging processes of yeast.
Subcell Biochem. 2012
Carmona-Gutierrez D, Reisenbichler A, Heimbucher P, Bauer MA, Braun RJ, Ruckenstuhl C, Büttner S, Eisenberg T, Rockenfeller P, Fröhlich KU, Kroemer G, Madeo F.
Ceramide triggers metacaspase-independent mitochondrial cell death in yeast.
Cell Cycle. 2011
Swinnen E, Büttner S, Outeiro TF, Galas MC, Madeo F, Winderickx J, Franssens V.
Aggresome formation and segregation of inclusions influence toxicity of α-synuclein and synphilin-1 in yeast.
Biochem Soc Trans. 2011
Haemmerle G, Moustafa T, Woelkart G, Büttner S, Schmidt A, van de Weijer T, Hesselink M, Jaeger D, Kienesberger PC, Zierler K, Schreiber R, Eichmann T, Kolb D, Kotzbeck P, Schweiger M, Kumari M, Eder S, Schoiswohl G, Wongsiriroj N, Pollak NM, Radner FP, Preiss-Landl K, Kolbe T, Rülicke T, Pieske B, Trauner M, Lass A, Zimmermann R, Hoefler G, Cinti S, Kershaw EE, Schrauwen P, Madeo F, Mayer B, Zechner R.
ATGL-mediated fat catabolism regulates cardiac mitochondrial function via PPAR-α and PGC-1.
Nat Med. 2011
Büttner S, Ruli D, Vögtle FN, Galluzzi L, Moitzi B, Eisenberg T, Kepp O, Habernig L, Carmona-Gutierrez D, Rockenfeller P, Laun P, Breitenbach M, Khoury C, Fröhlich KU, Rechberger G, Meisinger C, Kroemer G, Madeo F.
A yeast BH3-only protein mediates the mitochondrial pathway of apoptosis.
EMBO J. 2011
Braun RJ, Sommer C, Carmona-Gutierrez D, Khoury CM, Ring J, Büttner S, Madeo F.
Neurotoxic 43-kDa TAR DNA-binding protein (TDP-43) triggers mitochondrion-dependent programmed cell death in yeast.
J Biol Chem. 2011 Jun 3;286(22):19958-72.
Carmona-Gutiérrez D, Bauer MA, Ring J, Knauer H, Eisenberg T, Büttner S, Ruckenstuhl C, Reisenbichler A, Magnes C, Rechberger GN, Birner-Gruenberger R, Jungwirth H, Fröhlich KU, Sinner F, Kroemer G, Madeo F.
The propeptide of yeast cathepsin D inhibits programmed necrosis.
Cell Death Dis. 2011
Galluzzi L, Vanden Berghe T, Vanlangenakker N, Buettner S, Eisenberg T, Vandenabeele P, Madeo F, Kroemer G.
Programmed necrosis from molecules to health and disease.
Int Rev Cell Mol Biol. 2011
Büttner S, Delay C, Franssens V, Bammens T, Ruli D, Zaunschirm S, de Oliveira RM, Outeiro TF, Madeo F, Buée L, Galas MC, Winderickx J.
Synphilin-1 enhances α-synuclein aggregation in yeast and contributes to cellular stress and cell death in a Sir2-dependent manner.
PLoS One. 2010
Rockenfeller P, Ring J, Muschett V, Beranek A, Buettner S, Carmona-Gutierrez D, Eisenberg T, Khoury C, Rechberger G, Kohlwein SD, Kroemer G, Madeo F.
Fatty acids trigger mitochondrion-dependent necrosis.
Cell Cycle. 2010
Carmona-Gutierrez D, Ruckenstuhl C, Bauer MA, Eisenberg T, Büttner S, Madeo F.
Cell death in yeast: growing applications of a dying buddy.
Cell Death Differ. 2010
Carmona-Gutierrez D, Eisenberg T, Büttner S, Meisinger C, Kroemer G, Madeo F.
Apoptosis in yeast: triggers, pathways, subroutines.
Cell Death Differ. 2010
Franssens V, Boelen E, Anandhakumar J, Vanhelmont T, Büttner S, Winderickx J.
Yeast unfolds the road map toward alpha-synuclein-induced cell death.
Cell Death Differ. 2010
Eisenberg T, Carmona-Gutierrez D, Büttner S, Tavernarakis N, Madeo F.
Necrosis in yeast.
Apoptosis. 2010
Braun RJ, Büttner S, Ring J, Kroemer G, Madeo F.
Nervous yeast: modeling neurotoxic cell death.
Trends Biochem Sci. 2010
Madeo F, Eisenberg T, Büttner S, Ruckenstuhl C, Kroemer G.
Spermidine: a novel autophagy inducer and longevity elixir.
Autophagy. 2010
Eisenberg T, Knauer H, Schauer A, Büttner S, Ruckenstuhl C, Carmona-Gutierrez D, Ring J, Schroeder S, Magnes C, Antonacci L, Fussi H, Deszcz L, Hartl R, Schraml E, Criollo A, Megalou E, Weiskopf D, Laun P, Heeren G, Breitenbach M, Grubeck-Loebenstein B, Herker E, Fahrenkrog B, Fröhlich KU, Sinner F, Tavernarakis N, Minois N, Kroemer G, Madeo F.
Induction of autophagy by spermidine promotes longevity.
Nat Cell Biol. 2009
Madeo F, Carmona-Gutierrez D, Ring J, Büttner S, Eisenberg T, Kroemer G.
Caspase-dependent and caspase-independent cell death pathways in yeast.
Biochem Biophys Res Commun. 2009
Ruckenstuhl C, Büttner S, Carmona-Gutierrez D, Eisenberg T, Kroemer G, Sigrist SJ, Fröhlich KU, Madeo F.
The Warburg effect suppresses oxidative stress induced apoptosis in a yeast model for cancer.
PLoS One. 2009
Jungwirth H, Ring J, Mayer T, Schauer A, Büttner S, Eisenberg T, Carmona-Gutierrez D, Kuchler K, Madeo F.
Loss of peroxisome function triggers necrosis.
FEBS Lett. 2008
Low CP, Shui G, Liew LP, Büttner S, Madeo F, Dawes IW, Wenk MR, Yang H.
Caspase-dependent and -independent lipotoxic cell-death pathways in fission.
J Cell Sci. 2008
Büttner S, Bitto A, Ring J, Augsten M, Zabrocki P, Eisenberg T, Jungwirth H, Hutter S, Carmona-Gutierrez D, Kroemer G, Winderickx J, Madeo F.
Functional mitochondria are required for alphasynuclein toxicity in aging yeast.
J Biol Chem. 2008
Almeida B, Büttner S, Ohlmeier S, Silva A, Mesquita A, Sampaio-Marques B, Osório NS, Kollau A, Mayer B, Leão C, Laranjinha J, Rodrigues F, Madeo F, Ludovico P.
NO-mediated apoptosis in yeast.
J Cell Sci. 2007
Büttner S, Carmona-Gutierrez D, Vitale I, Castedo M, Ruli D, Eisenberg T, Kroemer G, Madeo F.
Depletion of endonuclease G selectively kills polyploid cells.
Cell Cycle. 2007
Eisenberg T, Büttner S, Kroemer G, Madeo F.
The mitochondrial pathway in yeast apoptosis.
Apoptosis. 2007
Büttner S, Carmona-Gutierrez D, Eisenberg T, Ruli D, Madeo F.
Conspiracy of yeast killers: the fifth international meeting on yeast apoptosis in Prague, Czech Republic.
FEMS Yeast Res. 2007
Büttner S, Eisenberg T, Carmona-Gutierrez D, Ruli D, Knauer H, Ruckenstuhl C, Sigrist C, Wissing S, Kollroser M, Fröhlich KU, Sigrist S, Madeo F.
Endonuclease G regulates budding yeast life and death.
Mol Cell. 2007
Büttner S, Eisenberg T, Herker E, Carmona-Gutierrez D, Kroemer G, Madeo F.
Why yeast cells can undergo apoptosis: death in times of peace, love, and war.
J Cell Biol. 2006
Braun RJ, Zischka H, Madeo F, Eisenberg T, Wissing S, Büttner S, Engelhardt SM, Büringer D, Ueffing M.
Crucial mitochondrial impairment upon CDC48 mutation in apoptotic yeast.
J Biol Chem. 2006
Allen C, Büttner S, Aragon AD, Thomas JA, Meirelles O, Jaetao JE, Benn D, Ruby SW, Veenhuis M, Madeo F, Werner-Washburne M.
Isolation of quiescent and nonquiescent cells from yeast stationary-phase cultures.
J Cell Biol. 2006
Wissing S, Ludovico P, Herker E, Büttner S, Engelhardt SM, Decker T, Link A, Proksch A, Rodrigues F, Corte-Real M, Fröhlich KU, Manns J, Candé C, Sigrist SJ, Kroemer G, Madeo F.
An AIF orthologue regulates apoptosis in yeast.
J Cell Biol. 2004
Herker E, Jungwirth H, Lehmann KA, Maldener C, Fröhlich KU, Wissing S, Büttner S, Fehr M, Sigrist S, Madeo F.
Chronological aging leads to apoptosis in yeast.
J Cell Biol. 2004

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