Mechanisms of Action of FUNDC1 in Cerebral Ischemia-Reperfusion Injury

Cerebral ischemia-reperfusion injury (CIRI) refers to a cascade of pathological events initiated by the restoration of blood flow to ischemic brain regions in patients with cerebral infarction. This process leads to mitochondrial dysfunction through mechanisms including oxidative stress, calcium overload, inflammation, and impaired energy metabolism. FUN14 domain containing 1 (FUNDC1), a key receptor protein involved in mitochondrial autophagy, plays a crucial protective role in CIRI by regulating mitophagy and maintaining mitochondrial quality control. This function is governed by the dynamic phosphorylation and dephosphorylation of FUNDC1, which finely modulate the activation and inhibition of mitophagy, thereby attenuating mitochondrial dysfunction. Moreover, FUNDC1 is implicated in mitochondrial fission, the clearance of unfolded proteins, mitochondrial iron metabolism, and inter-organelle communication, collectively contributing to the regulation of cellular metabolism and immune responses. Therefore, targeting FUNDC1-mediated mitophagy to restore mitochondrial quality control and reduce mitochondrial dysfunction represents a promising therapeutic strategy for CIRI. This review summarizes the role of FUNDC1 in mitochondrial dynamic homeostasis, inter-organelle communication, and CIRI, highlighting its potential as a therapeutic target.