How the Mitoprotein-Induced Stress Response Safeguards the Cytosol: A Unified View. Issue 3 (March 2020) - Boos, Felix
Abstract : Mitochondrial and cytosolic proteostasis are of central relevance for cellular stress resistance and organismal health. Recently, a number of individual cellular programs were described that counter the fatal consequences of mitochondrial dysfunction. These programs remove arrested import intermediates from mitochondrial protein translocases, stabilize protein homeostasis within mitochondria, and, in particular, increase the levels and activity of chaperones and the proteasome system in the cytosol. Here, we describe the different responses to mitochondrial perturbation and propose to unify the seemingly distinct mitochondrial-cytosolic quality control mechanisms into a single network, the mitoprotein-induced stress response. This holistic view places mitochondrial biogenesis at a central position of the cellular proteostasis network, emphasizing the importance of mitochondrial protein import processes for development, reproduction, and ageing. Highlights: Owing to their post-translational mode of import, mitochondrial precursor proteins represent a significant challenge to the cells' ability to maintain cytosolic proteostasis, particularly when the amount of cytosolic precursors exceeds the import capacity of mitochondria. Mitoprotein-induced stress elicits a complex regulatory network that: (i) removes stalled precursors from the mitochondrial surface, (ii) slows down the synthesis of mitochondrial proteins, and (iii) increases the levels of chaperones and proteases and attenuates cytosolic translation. Seemingly disparate reactions to mitochondrial stress are integrated into a general mitoprotein-induced stress response that couples 'mitochondria-centric' adaptations with general stress programs such as the heat shock response.