Mitochondrial iron regulation as an emerging target in ischemia/reperfusion injury during kidney transplantation

The injury caused by ischemia and subsequent reperfusion (I/R) is inevitable during kidney transplantation and its current management remains unsatisfactory. Iron is considered to play a remarkable pathologic role in the initiation or progression of tissue damage induced by I/R, whereas the effects of iron-related therapy remain controversial owing to the complicated nature of iron's involvement in multiple biological processes. A significant portion of the cellular iron is located in the mitochondria, which exerts a central role in the development and progression of I/R injury. Recent studies of iron regulation associated with mitochondrial function represents a unique opportunity to improve our knowledge on the pathophysiology of I/R injury. However, the molecular mechanisms linking mitochondria to the iron homeostasis remain unclear. In this review, we provide a comprehensive analysis of the alterations to iron metabolism in I/R injury during kidney transplantation, analyze the current understanding of mitochondrial regulation of iron homeostasis and discussed its potential application in I/R injury. The elucidation of regulatory mechanisms regulating mitochondrial iron homeostasis will offer valuable insights into potential therapeutic targets for alleviating I/R injury with the ultimate aim of improving kidney graft outcomes, with potential implications that could also extend to acute kidney injury or other I/R injuries.