Abstract
Depression is the most disabling neuropsychiatric disorder, but its exact mechanisms remain unclear. Mitochondrial energy metabolism may play a key role in the onset and development of depression. Cytokines such as PGC-1α, NLRP3, and BDNF can influence mitochondrial energy metabolism by regulating mitochondrial biogenesis, immune inflammation, and neuroplasticity, thereby mediating the occurrence and progression of depression. Exercise can improve depression by regulating mitochondrial energy metabolism. The molecular mechanisms are closely related to the upregulation of exercise-induced PGC-1α, AMPK, SIRT1, and BDNF expression, as well as the downregulation of NLRP3 expression. These factors can activate key factors or pathways such as Nrf2, AMPK, and PKA/CREB, while inhibiting the excessive activation of NF-κB. Through these mechanisms, they regulate the expression of downstream target genes (such as TFAM, NRF1, CREB, and Bcl-2), thereby enhancing mitochondrial biogenesis and improving the quantity and quality of mitochondria. Additionally, they can act to inhibit the release of inflammatory factors to improve immune inflammation, enhance neuroplasticity, promote neuronal growth, and facilitate synapse formation and remodeling, thereby enhancing mitochondrial energy metabolism and improving its dysfunction, which in turn alleviates depression. Currently, there is a lack of systematic and comprehensive research on the mechanisms by which exercise improves depression through mitochondrial energy metabolism. Therefore, this article aims to review and analyze the role of mitochondrial energy metabolism in the improvement of depression through exercise, in order to provide a new theoretical basis and research ideas for the prevention and treatment of depression.