Mitochondrial dynamics in depression: friend or foe?

Depression represents a significant global health burden characterized by complex, multifactorial pathophysiology. While traditional theories have focused on monoamine neurotransmitter imbalances, emerging evidence implicates mitochondrial dysfunction as a critical contributor to depressive disorders. This review examines the bidirectional relationship between mitochondrial dynamics, fusion, fission, biogenesis, and mitophagy and depression pathophysiology. The study synthesizes recent preclinical and clinical findings demonstrating alterations in mitochondrial morphology and dynamics in depressed subjects and explores the paradoxical nature of these changes, which can serve both adaptive and maladaptive roles. The review further evaluates therapeutic approaches targeting mitochondrial dynamics, including conventional antidepressants, lifestyle interventions, and novel mitochondria-targeted compounds. Ultimately, the relationship between mitochondria and depression is explained to serve as enlightenment and to find better approaches for using mitochondrial approaches in therapy for Depression.