We are interested in different aspects of cellular aging and organellar connectivity. Using a combination of molecular and cell biology, genetics, biochemistry and imaging, we apply yeast as a model to understand age-associated cellular decay. The causes of aging are intertwined, and interdependent organelle subsystems and networks cooperate to sustain viability over time. Communication between organelles is ensured by dedicated signal transduction pathways or by direct physical contact at membrane contact sites (MCS). We are interested in contact dynamics in response to aging, altered metabolic regimes and cell stress and the impact of organellar communication on cellular fitness and proteostasis in aging cells. The capacity of a cell to balance protein synthesis, folding and degradation progressively declines during aging, and long-lived cells are particularly sensitive to the deterioration of protein quality control. The accumulation of abnormal proteins in the course of aging expedites the sequential decay of different proteostatic subsystems maintaining cellular homeostasis, including autophagy. The different projects in our lab are centered around interorganellar communication, facilitated by signal transduction pathways and by direct physical contact between distinct organelles.
Virtually all organelles within a cell are connected by MCS, and such physical interaction facilitates interorganellar communication and the integration of compartmentalized processes by exchange of metabolites, lipids and ions. Moreover, MCS promote the formation of lipid rafts and are associated with misfolded and aggregating proteins. We are interested in MCS dynamics, molecular architecture and abundance in response to aging and cellular stress and the function of MCS in different aspects of proteostasis. In addition, we study how different nutritional regimes, ranging from caloric restriction and phosphate restriction to fermentative vs respiratory carbon sources, affect interorganellar connectivity and organellar function. Our aim is to provide insights into yet unexplored functions of these MCS in cellular homeostasis during aging.
In a national consortium (groups Nyström, Höög, Ott, Andréasson, Büttner), we aim to map how interconnected protein quality control changes genetically, functionally, and structurally during aging and thus affects lifespan, a collaborative project funded by the Knut and Alice Wallenberg foundation.
Keywords
Cellular aging; intracellular communication; membrane contact sites; yeast; proteostasis; autophagy; interconnected quality control; cellular stress; cell death;
Selected publications
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 Oct 5;:e51015.
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 Jul 28;32(4):107972.
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 Feb 5;7(4):106-114.
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 Jan 2;77(1):180-188.e9.
Andréasson C, Ott M, Büttner S. Mitochondria orchestrate proteostatic and metabolic stress responses. EMBO Rep. 2019 Oct 4;20(10):e47865.
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;11:205.
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 Jun 5;27(6):1309-1322.e6.
