AG Büttner - Cell Biology

 

Cellular aging and organelle connectivity

Our main research focus is intracellular communication during cellular aging, stress and metabolic adaptation. A eukaryotic cell is organized as an interconnected network of membrane-delimited organelles that communicate via different means. A prominent mechanism for organelle connectivity is direct physical contact via so-called membrane contact sites, established by dedicated tethering machineries via protein-protein and protein-lipid interactions. Virtually all organelles are connected by membrane contact sites, and such physical interaction facilitates the integration of compartmentalized processes by exchange of metabolites, lipids and ions.

Membrane contact sites are in a prime position to connect different proteostasis subsystems and thus might represent critical nodes to maintain and fine-tune mitochondrial, cytosolic and ER-localized proteostasis subsystems, thereby ensuring cellular fitness over time. 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, leading to the accumulation of protein aggregates. We are interested in how the accumulation of abnormal and proteotoxic proteins in the course of aging contributes to the sequential decay of different proteostasis subsystems and how direct organellar contact contributes to the maintenance of cellular proteostasis.

To unravel how organelle connectivity contributes to protein and lipid homeostasis during stress and aging, we use yeast as a genetically-tractable model organism and a combination of molecular and cell biology, genetics, biochemistry and imaging techniques. We complement our studies in yeast, a model which has led the way for fundamental molecular concepts of organellar tethering, with Drosophila research to extend our findings from the cellular to the organismal level.