Mitochondrial unfolded protein response in ischemia-reperfusion injury

Mitochondrial unfolded protein response (UPRmt) is a mitochondrial stress response that activates the tran-scriptional program of mitochondrial chaperone proteins and proteases to keep protein homeostasis in mito-chondria. Ischemia-reperfusion injury results in multiple severe clinical issues linked to high morbidity and mortality in various disorders. The pathophysiology and pathogenesis of ischemia-reperfusion injury are com-plex and multifactorial. Emerging evidence showed the roles of UPRmt signaling in ischemia-reperfusion injury. Herein, we discuss the regulatory mechanisms underlying UPRmt signaling in C. elegans and mammals. Furthermore, we review the recent studies into the roles and mechanisms of UPRmt signaling in ische-mia-reperfusion injury of the heart, brain, kidney, and liver. Further research of UPRmt signaling will potentially develop novel therapeutic strategies against ischemia-reperfusion injury.