The role of mitophagy in perioperative neurocognitive disorder: from mechanisms to implications

Perioperative neurocognitive disorder (PND) is a significant neurological complication in aging perioperativepatients, seriously impacting their postoperative recovery and cognition as well as quality of life. The occurrence of PND is closely related to various factors, including neuroinflammation and oxidative stress, while the exact mechanism is still unknown. Mitophagy is a specialized form of autophagy and maintains cellular homeostasis by selectively degrading damaged and dysfunctional mitochondria, serving as a crucial quality control mechanism to ensure the mitochondrial network's integrity and functionality. Mitophagy has been proved to be involved in the onset and progression of major neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. Recently, findings indicated that mitophagy may also play critical roles in the pathogenesis of PND, and the mechanisms may involve ubiquitin-dependent pathways (such as the PINK1/Parkin pathway) and non-ubiquitin-dependent pathways (such as the BNIP3/FUNDC1 pathway). Studies indicated that the PINK1/Parkin pathway is impaired in the animal PND models. In contrast, the BNIP3/ FUNDC1 pathway is neuroprotective by promoting mitophagy under stress conditions such as hypoxia. In addition, abnormal Tau protein aggregation and ferroptosis are correlated with mitophagy and PND in animal studies. In this review, we focused on the role and detailed mechanism of mitophagy in the occurrence and development of PND, as well as on possible potential targets involving mitophagy modulation.