Mild Hypothermia Alleviates Ischemia and Reperfusion Injury by Activating PINK1/Parkin Mitophagy

Ischemia-reperfusion (IR) injury is characterized by significant neuronal apoptosis and mitochondrial damage.Despite significant advancements in understanding the pathophysiological mechanisms of IR, effective therapeutic strategies remain limited. Previous studies have shown that mild hypothermia (MH) can significantly alleviate brain IR injury by reducing neuronal apoptosis and mitochondrial damage, while mitophagy plays a crucial role in maintaining cellular self-protection and mitochondrial homeostasis. However, the involvement of the PINK1/Parkin signaling pathway, a classical regulatory route for mitophagy, in the protective effects of MH against IR remains unclear. To investigate this phenomenon, we used neuron-like SH-SY5Y cells and employed an oxygen-glucose deprivation/reoxygenation (OGD/R) model to simulate the in vitro IR process, and conducted a series of cell experiments. Our results demonstrated that under MH conditions, the expression levels of PINK1 and Parkin were upregulated after 5 h of ischemia-hypoxia followed by 24 h of reoxygenation, and the protective effect on cells was also significant. Furthermore, the inhibition of the mitophagy pathway may partially eliminate the protective effect provided by MH against OGD/R-induced damage.These findings indicate that the protective effects of MH against IR is mediated, at least in part, through the PINK1/Parkin-dependent mitophagy pathway.This study provides new insights into the mechanisms by which MH mitigates IR injury and may offer potential therapeutic targets for treating IR-related diseases.