Sirtuin 3, a mitochondrial metabolic enzyme, links the mitochondrial function to neurophysiology in depression.

Depression, characterized by sustained low moods and even suicidal tendencies, has been intimately linked with mitochondrial dysfunction. This dysfunction is significantly connected with various psychiatric disorders, suggesting its potential role in the pathogenesis and progression of depression. Sirtuin 3 (SIRT3), a potent deacetylase enzyme primarily located within mitochondria, orchestrates mitochondrial function and mitigates various dysfunctions, e.g., insufficient cellular energy supply and oxidative stress. Insufficient cellular energy supply and oxidative stress disrupt normal neuroplasticity and neuroinflammation in the nervous system, as well as disturbances of the hypothalamic-pituitary-adrenal axis in peripheral systems. This review aims to elucidate that SIRT3 can be a potential target for depression, thereby summarizing the mechanisms by which SIRT3 is involved in the pathogenesis and progression of depression by regulating mitochondrial function.