Signaling and Regulation of the Mitochondrial Unfolded Protein Response
2019
: The mitochondrial proteome encompasses more than a thousand proteins, which are encoded by the mitochondrial and nuclear genomes. Mitochondrial biogenesis and network health relies on maintenance of protein import pathways and the protein-folding environment. Cell-extrinsic or -intrinsic stressors that challenge mitochondrial proteostasis negatively affect organellar function. During conditions of stress, cells use impaired protein import as a sensor for mitochondrial dysfunction to activate a stress response called the mitochondrial unfolded protein response (UPRmt). UPRmt activation leads to an adaptive transcriptional program that promotes mitochondrial recovery, metabolic adaptations, and innate immunity. In this review, we discuss the regulation of UPRmt activation as well as its role in maintaining mitochondrial homeostasis in physiological and pathological scenarios.
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