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Mitochondrial defects can cause a variety of human diseases and protective mechanisms exist to maintain mitochondrial functionality. Imbalances in mitochondrial proteostasis trigger a transcriptional program, termed mitochondrial unfolded protein response (mtUPR). However, the temporal sequence of events in mtUPR is unclear and the consequences on mitochondrial protein import are controversial. Here, we have quantitatively analyzed all main import pathways into mitochondria after different time spans of mtUPR induction. Kinetic analyses reveal that protein import into all mitochondrial subcompartments strongly increases early upon mtUPR and that this is accompanied by rapid remodelling of the mitochondrial signature lipid cardiolipin. Genetic inactivation of cardiolipin synthesis precluded stimulation of protein import and compromised cellular fitness. At late stages of mtUPR upon sustained stress, mitochondrial protein import efficiency declined. Our work clarifies the enigma of protein import upon mtUPR and identifies sequential mtUPR stages, in which an early increase in protein biogenesis to restore mitochondrial proteostasis is followed by late stages characterized by a decrease in import capacity upon prolonged stress induction.
Daniel Poveda-Huertes; Asli Aras Taskin; Ines Dhaouadi; Lisa Myketin; Adinarayana Marada; Lukas Habernig; Sabrina Büttner; F.-Nora Vögtle. Increased mitochondrial protein import and cardiolipin remodelling upon early mtUPR. PLOS Genetics 2021, 17, e1009664 .
AMA StyleDaniel Poveda-Huertes, Asli Aras Taskin, Ines Dhaouadi, Lisa Myketin, Adinarayana Marada, Lukas Habernig, Sabrina Büttner, F.-Nora Vögtle. Increased mitochondrial protein import and cardiolipin remodelling upon early mtUPR. PLOS Genetics. 2021; 17 (7):e1009664.
Chicago/Turabian StyleDaniel Poveda-Huertes; Asli Aras Taskin; Ines Dhaouadi; Lisa Myketin; Adinarayana Marada; Lukas Habernig; Sabrina Büttner; F.-Nora Vögtle. 2021. "Increased mitochondrial protein import and cardiolipin remodelling upon early mtUPR." PLOS Genetics 17, no. 7: e1009664.
Editorial on the Research Topic Modeling Neurodegeneration in Yeast 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. The review of Ruetenik and Barrientos provides an overview of the advantages of post-mitotic yeast cultures to model neurodegenerative protein misfolding disorders and summarizes suitable methodology. Thus, this manuscript is of special interest for people new to the field. The reviews from Schneider et al. and Rothe et al. describe the distinct cellular protein quality control compartments in which human disease-associated and aggregation-prone proteins are deposited and discuss why and in which cellular context specific proteotoxic proteins prefer distinct quality control compartments. The reviews from Hofer et al. and Zheng et al. address yeast models for Huntington's disease (HD), for which many yeast models have been developed so far. The manuscripts give a comprehensive and critical overview of the applied yeast models expressing fragments of the human protein huntingtin, responsible for HD. They describe how these models can be used for pharmacological approaches, and include a mitochondria-associated perspective on Huntington's disease. Di Gregorio et al., Monahan et al., and Lindström and Liu critically review yeast models for amyotrophic lateral sclerosis (ALS), the most common motoneuron disease. They summarize how yeast ALS models expressing the common ALS-associated proteins TDP-43 and FUS have been successfully used to unravel the molecular mechanisms underlying disease progression. For Alzheimer's disease (AD), the Research Topic comprises three original studies. One of the pathological hallmarks of AD is the accumulation of the small hydrophobic peptide β-amyloid exerting extra- and intracellular toxicity (Goedert and Spillantini, 2006). Chen et al. and Fruhmann et al. use yeast β-amyloid models to elucidate the intricate interplay between energetics, ER stress and β-amyloid toxicity, with a particular focus on the pathophysiological membrane lesions triggered by β-amyloid. Besides β-amyloid, a mutant variant of ubiquitin, namely UBB+1, accumulates in disease-affected neurons in AD. High levels of UBB+1 have been described to be detrimental in neurons and yeast cells (Braun et al., 2015). Using yeast expressing UBB+1, Muñoz-Arellano et al. challenge this paradigm, showing that UBB+1 expression can induce a beneficial stress response. Thus, depending on the cellular context, UBB+1 may also enable the cells to cope with proteotoxic stress, which has been confirmed by a more recent study (Verheijen et al., 2020). For Parkinson's disease (PD), two original studies are included in the Research Topic. Popova et al. provides novel insights on β-synuclein, a homolog of the PD-associated protein α-synuclein. The authors observed that β-synuclein, just as α-synuclein, triggers toxicity in yeast. Of interest, post-translational modification of β-synuclein, namely sumoylation, protects cells from this toxicity. Aufschnaiter et al. worked with another important PD-associated protein, the protein kinase LRRK2. The authors could show that the enzymatic core of this protein compromises mitochondrial function in yeast. While general mitochondrial dysfunction is a well-established hallmark for PD, this study demonstrates that LRRK2 inhibits mitochondrial biogenesis, thus providing a novel perspective on cellular demise during PD. Finally, Verma et al. could show in their original study that the aggregation of human transthyretin is modulated by yeast prions, thereby confirming the strong interaction of this human protein with the yeast quality control system. Collectively, this Research Topic highlights the power of yeast models to understand fundamental molecular mechanisms contributing to human proteopathies. We would like to thank all the authors and reviewers contributing to this project. We anticipate numerous novel findings, relevant for human neurodegenerative disorders, based on...
Ralf J. Braun; Sabrina Büttner. Editorial: Modeling Neurodegeneration in Yeast. Frontiers in Molecular Neuroscience 2021, 14, 1 .
AMA StyleRalf J. Braun, Sabrina Büttner. Editorial: Modeling Neurodegeneration in Yeast. Frontiers in Molecular Neuroscience. 2021; 14 ():1.
Chicago/Turabian StyleRalf J. Braun; Sabrina Büttner. 2021. "Editorial: Modeling Neurodegeneration in Yeast." Frontiers in Molecular Neuroscience 14, no. : 1.
SummaryMembrane 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.
Sergi Tosal-Castano; Carlotta Peselj; Verena Kohler; Lukas Habernig; Lisa Larsson Berglund; Mahsa Ebrahimi; F.-Nora Vögtle; Johanna Höög; Claes Andréasson; Sabrina Büttner. Snd3 controls nucleus-vacuole junctions in response to glucose signaling. Cell Reports 2021, 34, 108637 .
AMA StyleSergi Tosal-Castano, Carlotta Peselj, Verena Kohler, Lukas Habernig, Lisa Larsson Berglund, Mahsa Ebrahimi, F.-Nora Vögtle, Johanna Höög, Claes Andréasson, Sabrina Büttner. Snd3 controls nucleus-vacuole junctions in response to glucose signaling. Cell Reports. 2021; 34 (3):108637.
Chicago/Turabian StyleSergi Tosal-Castano; Carlotta Peselj; Verena Kohler; Lukas Habernig; Lisa Larsson Berglund; Mahsa Ebrahimi; F.-Nora Vögtle; Johanna Höög; Claes Andréasson; Sabrina Büttner. 2021. "Snd3 controls nucleus-vacuole junctions in response to glucose signaling." Cell Reports 34, no. 3: 108637.
Cellular adaptation to stress and metabolic cues requires a coordinated response of different intracellular compartments, separated by semipermeable membranes. One way to facilitate interorganellar communication is via membrane contact sites, physical bridges between opposing organellar membranes formed by an array of tethering machineries. These contact sites are highly dynamic and establish an interconnected organellar network able to quickly respond to external and internal stress by changing size, abundance and molecular architecture. Here, we discuss recent work on nucleus-vacuole junctions, connecting yeast vacuoles with the nucleus. Appearing as small, single foci in mitotic cells, these contacts expand into one enlarged patch upon nutrient exhaustion and entry into quiescence or can be shaped into multiple large foci essential to sustain viability upon proteostatic stress at the nuclear envelope. We highlight the remarkable plasticity and rapid remodelling of these contact sites upon metabolic or proteostatic stress and their emerging importance for cellular fitness.
Verena Kohler; Sabrina Büttner. Remodelling of Nucleus-Vacuole Junctions During Metabolic and Proteostatic Stress. Contact 2021, 4, 1 .
AMA StyleVerena Kohler, Sabrina Büttner. Remodelling of Nucleus-Vacuole Junctions During Metabolic and Proteostatic Stress. Contact. 2021; 4 ():1.
Chicago/Turabian StyleVerena Kohler; Sabrina Büttner. 2021. "Remodelling of Nucleus-Vacuole Junctions During Metabolic and Proteostatic Stress." Contact 4, no. : 1.
In response to cellular stress and damage, certain tissues are able to regenerate and to restore tissue homeostasis. In Drosophila imaginal wing discs, dying cells express mitogens that induce compensatory proliferation in the surrounding tissue. Here we report that high levels of the BTB/POZ transcription factor Bab2 in the posterior compartment of wing discs activates c-Jun N-terminal kinase (JNK) signaling and local, cell-autonomous apoptotic cell death. This in turn triggered the upregulation of the Dpp mitogen and cellular proliferation in the anterior compartment in a JNK-dependent manner. In the posterior compartment, however, dpp expression was suppressed, most likely by direct transcriptional repression by Bab2. This dual-mode of JNK-signaling, autocrine pro-apoptotic signaling and paracrine pro-proliferative signaling, led to opposite effects in the two compartments and reprogramming of the adult wing structure. We establish Bab2 as a regulator of wing disc development, with the capacity to reprogram development via JNK activation in a cell-autonomous and non-cell-autonomous manner.Summary statementZhao et al. shows that the BTB/POZ transcription factor Bab2 is a potent activator of JNK signaling, apoptosis and compensatory proliferation, thereby driving both pro-tumorigenic and anti-tumorigenic processes.
Yunpo Zhao; Jianli Duan; Alexis Dziedziech; Sabrina Büttner; Ylva Engström. Bab2 activates JNK signaling to reprogram Drosophila wing disc development. 2020, 1 .
AMA StyleYunpo Zhao, Jianli Duan, Alexis Dziedziech, Sabrina Büttner, Ylva Engström. Bab2 activates JNK signaling to reprogram Drosophila wing disc development. . 2020; ():1.
Chicago/Turabian StyleYunpo Zhao; Jianli Duan; Alexis Dziedziech; Sabrina Büttner; Ylva Engström. 2020. "Bab2 activates JNK signaling to reprogram Drosophila wing disc development." , no. : 1.
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.
Maria Cavinato; Corina T. Madreiter‐Sokolowski; Sabrina Büttner; Markus Schosserer; Werner Zwerschke; Sophia Wedel; Johannes Grillari; Wolfgang F. Graier; Pidder Jansen‐Dürr. Targeting cellular senescence based on interorganelle communication, multilevel proteostasis, and metabolic control. The FEBS Journal 2020, 288, 3834 -3854.
AMA StyleMaria Cavinato, Corina T. Madreiter‐Sokolowski, Sabrina Büttner, Markus Schosserer, Werner Zwerschke, Sophia Wedel, Johannes Grillari, Wolfgang F. Graier, Pidder Jansen‐Dürr. Targeting cellular senescence based on interorganelle communication, multilevel proteostasis, and metabolic control. The FEBS Journal. 2020; 288 (12):3834-3854.
Chicago/Turabian StyleMaria Cavinato; Corina T. Madreiter‐Sokolowski; Sabrina Büttner; Markus Schosserer; Werner Zwerschke; Sophia Wedel; Johannes Grillari; Wolfgang F. Graier; Pidder Jansen‐Dürr. 2020. "Targeting cellular senescence based on interorganelle communication, multilevel proteostasis, and metabolic control." The FEBS Journal 288, no. 12: 3834-3854.
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.
Jens Berndtsson; Andreas Aufschnaiter; Sorbhi Rathore; Lorena Marin‐Buera; Hannah Dawitz; Jutta Diessl; Verena Kohler; Antoni Barrientos; Sabrina Büttner; Flavia Fontanesi; Martin Ott. Respiratory supercomplexes enhance electron transport by decreasing cytochrome c diffusion distance. EMBO reports 2020, 21, e51015 .
AMA StyleJens Berndtsson, Andreas Aufschnaiter, Sorbhi Rathore, Lorena Marin‐Buera, Hannah Dawitz, Jutta Diessl, Verena Kohler, Antoni Barrientos, Sabrina Büttner, Flavia Fontanesi, Martin Ott. Respiratory supercomplexes enhance electron transport by decreasing cytochrome c diffusion distance. EMBO reports. 2020; 21 (12):e51015.
Chicago/Turabian StyleJens Berndtsson; Andreas Aufschnaiter; Sorbhi Rathore; Lorena Marin‐Buera; Hannah Dawitz; Jutta Diessl; Verena Kohler; Antoni Barrientos; Sabrina Büttner; Flavia Fontanesi; Martin Ott. 2020. "Respiratory supercomplexes enhance electron transport by decreasing cytochrome c diffusion distance." EMBO reports 21, no. 12: e51015.
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.
Alexandra Toth; Andreas Aufschnaiter; Olga Fedotovskaya; Hannah Dawitz; Pia Ädelroth; Sabrina Büttner; Martin Ott. Membrane-tethering of cytochrome c accelerates regulated cell death in yeast. Cell Death & Disease 2020, 11, 1 -16.
AMA StyleAlexandra Toth, Andreas Aufschnaiter, Olga Fedotovskaya, Hannah Dawitz, Pia Ädelroth, Sabrina Büttner, Martin Ott. Membrane-tethering of cytochrome c accelerates regulated cell death in yeast. Cell Death & Disease. 2020; 11 (9):1-16.
Chicago/Turabian StyleAlexandra Toth; Andreas Aufschnaiter; Olga Fedotovskaya; Hannah Dawitz; Pia Ädelroth; Sabrina Büttner; Martin Ott. 2020. "Membrane-tethering of cytochrome c accelerates regulated cell death in yeast." Cell Death & Disease 11, no. 9: 1-16.
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.
Verena Kohler; Andreas Aufschnaiter; Sabrina Büttner. Closing the Gap: Membrane Contact Sites in the Regulation of Autophagy. Cells 2020, 9, 1184 .
AMA StyleVerena Kohler, Andreas Aufschnaiter, Sabrina Büttner. Closing the Gap: Membrane Contact Sites in the Regulation of Autophagy. Cells. 2020; 9 (5):1184.
Chicago/Turabian StyleVerena Kohler; Andreas Aufschnaiter; Sabrina Büttner. 2020. "Closing the Gap: Membrane Contact Sites in the Regulation of Autophagy." Cells 9, no. 5: 1184.
Stable and destabilized GFP reporters to monitor calcineurin activity in Saccharomyces cerevisiae –
Jutta Diessl; Arpita Nandy; Christina Schug; Lukas Habernig; Sabrina Büttner. Stable and destabilized GFP reporters to monitor calcineurin activity in Saccharomyces cerevisiae. Microbial Cell 2020, 7, 106 -114.
AMA StyleJutta Diessl, Arpita Nandy, Christina Schug, Lukas Habernig, Sabrina Büttner. Stable and destabilized GFP reporters to monitor calcineurin activity in Saccharomyces cerevisiae. Microbial Cell. 2020; 7 (4):106-114.
Chicago/Turabian StyleJutta Diessl; Arpita Nandy; Christina Schug; Lukas Habernig; Sabrina Büttner. 2020. "Stable and destabilized GFP reporters to monitor calcineurin activity in Saccharomyces cerevisiae." Microbial Cell 7, no. 4: 106-114.
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.
Andreas Aufschnaiter; Verena Kohler; Shaden Khalifa; Aida Abd El-Wahed; Ming Du; Hesham El-Seedi; Sabrina Büttner. Apitoxin and Its Components against Cancer, Neurodegeneration and Rheumatoid Arthritis: Limitations and Possibilities. Toxins 2020, 12, 66 .
AMA StyleAndreas Aufschnaiter, Verena Kohler, Shaden Khalifa, Aida Abd El-Wahed, Ming Du, Hesham El-Seedi, Sabrina Büttner. Apitoxin and Its Components against Cancer, Neurodegeneration and Rheumatoid Arthritis: Limitations and Possibilities. Toxins. 2020; 12 (2):66.
Chicago/Turabian StyleAndreas Aufschnaiter; Verena Kohler; Shaden Khalifa; Aida Abd El-Wahed; Ming Du; Hesham El-Seedi; Sabrina Büttner. 2020. "Apitoxin and Its Components against Cancer, Neurodegeneration and Rheumatoid Arthritis: Limitations and Possibilities." Toxins 12, no. 2: 66.
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.
Nikolaos Charmpilas; Christoph Ruckenstuhl; Valentina Sica; Sabrina Büttner; Lukas Habernig; Silvia Dichtinger; Frank Madeo; Nektarios Tavernarakis; Jose Manuel Bravo-San Pedro; Guido Kroemer. Acyl-CoA-binding protein (ACBP): a phylogenetically conserved appetite stimulator. Cell Death & Disease 2020, 11, 1 -10.
AMA StyleNikolaos Charmpilas, Christoph Ruckenstuhl, Valentina Sica, Sabrina Büttner, Lukas Habernig, Silvia Dichtinger, Frank Madeo, Nektarios Tavernarakis, Jose Manuel Bravo-San Pedro, Guido Kroemer. Acyl-CoA-binding protein (ACBP): a phylogenetically conserved appetite stimulator. Cell Death & Disease. 2020; 11 (1):1-10.
Chicago/Turabian StyleNikolaos Charmpilas; Christoph Ruckenstuhl; Valentina Sica; Sabrina Büttner; Lukas Habernig; Silvia Dichtinger; Frank Madeo; Nektarios Tavernarakis; Jose Manuel Bravo-San Pedro; Guido Kroemer. 2020. "Acyl-CoA-binding protein (ACBP): a phylogenetically conserved appetite stimulator." Cell Death & Disease 11, no. 1: 1-10.
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.
Carmela Vazquez-Calvo; Tamara Suhm; Sabrina Büttner; Martin Ott. The basic machineries for mitochondrial protein quality control. Mitochondrion 2019, 50, 121 -131.
AMA StyleCarmela Vazquez-Calvo, Tamara Suhm, Sabrina Büttner, Martin Ott. The basic machineries for mitochondrial protein quality control. Mitochondrion. 2019; 50 ():121-131.
Chicago/Turabian StyleCarmela Vazquez-Calvo; Tamara Suhm; Sabrina Büttner; Martin Ott. 2019. "The basic machineries for mitochondrial protein quality control." Mitochondrion 50, no. : 121-131.
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.
Claes Andréasson; Martin Ott; Sabrina Büttner. Mitochondria orchestrate proteostatic and metabolic stress responses. EMBO reports 2019, 20, e47865 .
AMA StyleClaes Andréasson, Martin Ott, Sabrina Büttner. Mitochondria orchestrate proteostatic and metabolic stress responses. EMBO reports. 2019; 20 (10):e47865.
Chicago/Turabian StyleClaes Andréasson; Martin Ott; Sabrina Büttner. 2019. "Mitochondria orchestrate proteostatic and metabolic stress responses." EMBO reports 20, no. 10: e47865.
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.
Andreas Aufschnaiter; Sabrina Büttner. The vacuolar shapes of ageing: From function to morphology. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 2019, 1866, 957 -970.
AMA StyleAndreas Aufschnaiter, Sabrina Büttner. The vacuolar shapes of ageing: From function to morphology. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 2019; 1866 (5):957-970.
Chicago/Turabian StyleAndreas Aufschnaiter; Sabrina Büttner. 2019. "The vacuolar shapes of ageing: From function to morphology." Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 1866, no. 5: 957-970.
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.
Verena Kohler; Nikolaus Gössweiner-Mohr; Andreas Aufschnaiter; Christian Fercher; Ines Probst; Tea Pavkov-Keller; Kristin Hunger; Heimo Wolinski; Sabrina Büttner; Elisabeth Grohmann; Walter Keller. TraN: A novel repressor of an Enterococcus conjugative type IV secretion system. Nucleic Acids Research 2018, 46, 9201 -9219.
AMA StyleVerena Kohler, Nikolaus Gössweiner-Mohr, Andreas Aufschnaiter, Christian Fercher, Ines Probst, Tea Pavkov-Keller, Kristin Hunger, Heimo Wolinski, Sabrina Büttner, Elisabeth Grohmann, Walter Keller. TraN: A novel repressor of an Enterococcus conjugative type IV secretion system. Nucleic Acids Research. 2018; 46 (17):9201-9219.
Chicago/Turabian StyleVerena Kohler; Nikolaus Gössweiner-Mohr; Andreas Aufschnaiter; Christian Fercher; Ines Probst; Tea Pavkov-Keller; Kristin Hunger; Heimo Wolinski; Sabrina Büttner; Elisabeth Grohmann; Walter Keller. 2018. "TraN: A novel repressor of an Enterococcus conjugative type IV secretion system." Nucleic Acids Research 46, no. 17: 9201-9219.
Sabrina Büttner; Paula Ludovico; Karin Thevissen. From Regulated Cell Death to Adaptive Stress Strategies: Convergence and Divergence in Eukaryotic Cells. Oxidative Medicine and Cellular Longevity 2018, 2018, 1 -2.
AMA StyleSabrina Büttner, Paula Ludovico, Karin Thevissen. From Regulated Cell Death to Adaptive Stress Strategies: Convergence and Divergence in Eukaryotic Cells. Oxidative Medicine and Cellular Longevity. 2018; 2018 ():1-2.
Chicago/Turabian StyleSabrina Büttner; Paula Ludovico; Karin Thevissen. 2018. "From Regulated Cell Death to Adaptive Stress Strategies: Convergence and Divergence in Eukaryotic Cells." Oxidative Medicine and Cellular Longevity 2018, no. : 1-2.
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.
Andreas Aufschnaiter; Verena Kohler; Corvin Walter; Sergi Tosal-Castano; Lukas Habernig; Heimo Wolinski; Walter Keller; F.-Nora Vögtle; Sabrina Büttner. The Enzymatic Core of the Parkinson’s Disease-Associated Protein LRRK2 Impairs Mitochondrial Biogenesis in Aging Yeast. Frontiers in Molecular Neuroscience 2018, 11, 205 .
AMA StyleAndreas Aufschnaiter, Verena Kohler, Corvin Walter, Sergi Tosal-Castano, Lukas Habernig, Heimo Wolinski, Walter Keller, F.-Nora Vögtle, Sabrina Büttner. The Enzymatic Core of the Parkinson’s Disease-Associated Protein LRRK2 Impairs Mitochondrial Biogenesis in Aging Yeast. Frontiers in Molecular Neuroscience. 2018; 11 ():205.
Chicago/Turabian StyleAndreas Aufschnaiter; Verena Kohler; Corvin Walter; Sergi Tosal-Castano; Lukas Habernig; Heimo Wolinski; Walter Keller; F.-Nora Vögtle; Sabrina Büttner. 2018. "The Enzymatic Core of the Parkinson’s Disease-Associated Protein LRRK2 Impairs Mitochondrial Biogenesis in Aging Yeast." Frontiers in Molecular Neuroscience 11, no. : 205.
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.
Tamara Suhm; Jayasankar Mohanakrishnan Kaimal; Hannah Dawitz; Carlotta Peselj; Anna E. Masser; Sarah Hanzén; Matevž Ambrožič; Agata Smialowska; Markus L. Björck; Peter Brzezinski; Thomas Nyström; Sabrina Büttner; Claes Andréasson; Martin Ott. Mitochondrial Translation Efficiency Controls Cytoplasmic Protein Homeostasis. Cell Metabolism 2018, 27, 1309 -1322.e6.
AMA StyleTamara Suhm, Jayasankar Mohanakrishnan Kaimal, Hannah Dawitz, Carlotta Peselj, Anna E. Masser, Sarah Hanzén, Matevž Ambrožič, Agata Smialowska, Markus L. Björck, Peter Brzezinski, Thomas Nyström, Sabrina Büttner, Claes Andréasson, Martin Ott. Mitochondrial Translation Efficiency Controls Cytoplasmic Protein Homeostasis. Cell Metabolism. 2018; 27 (6):1309-1322.e6.
Chicago/Turabian StyleTamara Suhm; Jayasankar Mohanakrishnan Kaimal; Hannah Dawitz; Carlotta Peselj; Anna E. Masser; Sarah Hanzén; Matevž Ambrožič; Agata Smialowska; Markus L. Björck; Peter Brzezinski; Thomas Nyström; Sabrina Büttner; Claes Andréasson; Martin Ott. 2018. "Mitochondrial Translation Efficiency Controls Cytoplasmic Protein Homeostasis." Cell Metabolism 27, no. 6: 1309-1322.e6.
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.
Michael R. Yeaman; Sabrina Büttner; Karin Thevissen. Regulated Cell Death as a Therapeutic Target for Novel Antifungal Peptides and Biologics. Oxidative Medicine and Cellular Longevity 2018, 2018, 1 -20.
AMA StyleMichael R. Yeaman, Sabrina Büttner, Karin Thevissen. Regulated Cell Death as a Therapeutic Target for Novel Antifungal Peptides and Biologics. Oxidative Medicine and Cellular Longevity. 2018; 2018 ():1-20.
Chicago/Turabian StyleMichael R. Yeaman; Sabrina Büttner; Karin Thevissen. 2018. "Regulated Cell Death as a Therapeutic Target for Novel Antifungal Peptides and Biologics." Oxidative Medicine and Cellular Longevity 2018, no. : 1-20.