Fighting ischemia-reperfusion injury: Focusing on mitochondria-derived ferroptosis

Ischemia-reperfusion injury (IRI) is a major cause of mortality and morbidity. Current treatments for IRI have limited efficacy and novel therapeutic strategies are needed. Mitochondrial dysfunction not only initiates IRI but also plays a significant role in ferroptosis pathogenesis. Recent studies have highlighted that targeting mitochondrial pathways is a promising therapeutic approach for ferroptosis-induced IRI. The association between ferroptosis and IRI has been reviewed many times, but our review provides the first comprehensive overview with a focus on recent mitochondrial research. First, we present the role of mitochondria in ferroptosis. Then, we summarize the evidence on mitochondrial manipulation of ferroptosis in IRI and review recent therapeutic strategies aimed at targeting mitochondrial-related ferroptosis to mitigate IRI. We hope our review will provide new ideas for the treatment of IRI and accelerate the transition from bench to bedside.