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The mitochondrial unfolded protein response and its diverse roles in cellular stress

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PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biocel.2021.105934

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UPR; Mitochondria; Stress; Heart; Disease

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Mitochondrial function is crucial for cellular processes, and the mitochondrial unfolded protein response is a key mechanism for maintaining mitochondrial stability, aiding in cellular recovery by regulating other processes.
Mitochondrial function is centrally involved in many cellular processes, such as energy production, metabolism of nucleotides, amino acids, and lipids, calcium buffering, and regulation of cell death. Multiple mechanisms are engaged under conditions of mitochondrial dysfunction to restore cellular and, subsequently, systemic functions. The mitochondrial unfolded protein response is a homeostatic mechanism that has attracted a lot of interest recently and has been described in several organisms, including humans. The mitochondrial unfolded protein response serves as a first-line-of-defence mechanism against stress to restore mitochondrial proteostasis and functions. Here, we discuss the canonical mechanisms via which the mitochondrial unfolded protein response is activated under stress and examine recent evidence that links the response with other processes that promote survival and the recovery of the mitochondrial network (i.e. the integrated stress response and mitophagy).

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