Abstract

Balanced protein homeostasis (proteostasis) in the different cellular compartments is crucial to maintain function and survival. Proteostasis processes involve controlling protein folding, processing, and degradation. In mitochondria, protein import adds further complexity to proteostasis. Therefore, it is necessary to regulate both intra- and extra-mitochondrial processes to adjust mitochondrial proteostasis to varying conditions. The presentation will focus on our recent results that examine the interplay of protein quality control mechanisms across compartments. I will present data on the consequences of mitochondrial protein misfolding and the subsequent retrograde signaling via the mitochondrial unfolded protein response, adjustments in mitochondrial protein translation and import, and degradation of mitochondria by mitophagy. These processes are tightly integrated to ensure mitochondrial proteostasis. Furthermore, I will present new data on the role of mitochondrial proteostasis in replicative senescence. We found molecular links between perturbed stress signaling and mitochondrial dysfunction that act as key driver of senescence.