Mitochondrial unfolded protein response in ischemia-reperfusion injury

Mitochondrial unfolded protein response (UPR^mt) is a mitochondrial stress response that activates the transcriptional program of mitochondrial chaperone proteins and proteases to keep protein homeostasis in mitochondria. 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 complex and multifactorial. Emerging evidence showed the roles of UPR^mt signaling in ischemia-reperfusion injury. Herein, we discuss the regulatory mechanisms underlying UPR^mt signaling in C. elegans and mammals. Furthermore, we review the recent studies into the roles and mechanisms of UPR^mt signaling in ischemia-reperfusion injury of the heart, brain, kidney, and liver. Further research of UPR^mt signaling will potentially develop novel therapeutic strategies against ischemia-reperfusion injury.