Investigating the Antidepressant Mechanism of Acupuncture with a Focus on Mitochondrial Homeostasis

Background: Major depressive disorder (MDD) is a complex neuropsychiatric condition characterized by persistent low mood, reduced voluntary activity, and cognitive impairment. Mitochondria, often described as cellular power plants, play a fundamental role in maintaining normal neuronal function and emotional stability. Mitochondrial homeostasis encompasses multiple dimensions, including oxidative stress, apoptosis, biogenesis, and dynamics. Accumulating evidence indicates significant impairment of neuronal mitochondrial function in depressive patients, manifested as aberrant energy metabolism, exacerbated oxidative stress, and disrupted mitochondrial dynamics. Discussion: This narrative review synthesizes current evidence from both clinical and preclinical studies aims to explore the mechanisms by which acupuncture therapy restores mitochondrial homeostasis. Specifically, acupuncture ameliorates mitochondrial membrane permeability and structural integrity, enhances energy metabolism, attenuates damage induced by oxidative stress and mitophagy, and regulates mitochondrial dynamic processes (such as fission and fusion). These coordinated effects collectively constitute a key biological mechanism through which acupuncture exerts its antidepressant actions. Conclusion: This study elucidates a mechanism-based therapeutic strategy, clarifying how acupuncture counteracts depression through multi-target regulation of mitochondrial function. These findings underscore the translational value of acupuncture in clinical treatment regimens for major depressive disorder, offering a theoretical framework. Plain Language Summary: Acupuncture exerts antidepressant effects by restoring mitochondrial homeostasis, promoting neurogenesis, and reducing neuronal apoptosis. Key mechanisms involve regulating the mitochondrial permeability transition pore, balancing mitochondrial fission and fusion, enhancing mitochondrial biogenesis and mitophagy, and improving neuroplasticity. Studies indicate that acupuncture synergizes with conventional antidepressants by targeting shared mitochondrial pathways. Clinical evidence further supports acupuncture as an effective strategy for alleviating mitochondrial dysfunction in treatment-resistant depression. Keywords: major depressive disorder, mitochondria, mitochondrial stability, acupuncture, review