Mitochondrial damage is involved in many pathophysiological processes, such as tumor
development, metabolism, and neurodegenerative diseases. The mitochondrial unfolded protein
response (mtUPR) is the first stress-protective response initiated by mitochondrial damage, and it
repairs or clears misfolded proteins to alleviate this damage. Studies have confirmed that the sirtuin
family is essential for the mitochondrial stress response; in particular, SIRT1, SIRT3, and SIRT7
participate in the mtUPR in different axes. This article summarizes the associations of sirtuins with
the mtUPR as well as specific molecular targets related to the mtUPR in different disease models,
which will provide new inspiration for studies on mitochondrial stress, mitochondrial function
protection, and mitochondria-related diseases, such as neurodegenerative diseases.
Keywords: SIRT, mitochondrial unfolded protein response, mitochondrial stress, AMPK, FOXO3A, CHOP, PARP, mitochondrial
protein quality control.
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