Major depressive disorder (MDD) is one of the most prevalent stress-related mental disorders worldwide. Several biological mechanisms underlying the pathophysiology of MDD have been proposed, including endocrine disturbances, neurotransmitter deficits, impaired neuronal plasticity, and more recently, mitochondrial dysfunctions. In this review, we provide an overview of relevant molecular correlates of mitochondrial dysfunction in MDD, based on findings from clinical studies and stress-induced rodent models. We also compare differences and similarities between the phenotypes of MDD patients and animal models. Our analysis of the literature reveals that both MDD and stress are associated, in humans and animals, with changes in mitochondrial biogenesis, redox imbalance, increased oxidative damages of cellular macromolecules, and apoptosis. Yet, a considerable amount of conflicting data exist and therefore, the translation of findings from clinical and preclinical research to novel therapies for MDD remains complex. Further studies are needed to advance our understanding of the molecular networks and biological mechanisms involving mitochondria in the pathophysiology of MDD.

重度抑郁症 (MDD) 是全球最普遍的与压力相关的精神障碍之一。已经提出了 MDD 病理生理学的几种生物学机制，包括内分泌紊乱、神经递质缺陷、神经元可塑性受损，以及最近的线粒体功能障碍。在这篇综述中，我们根据临床研究和应激诱导的啮齿动物模型的发现，概述了 MDD 中线粒体功能障碍的相关分子相关性。我们还比较了 MDD 患者和动物模型的表型之​​间的差异和相似之处。我们对文献的分析表明，在人类和动物中，MDD 和压力都与线粒体生物发生的变化、氧化还原失衡、细胞大分子氧化损伤增加和细胞凋亡有关。然而，存在大量相互矛盾的数据，因此，将临床和临床前研究的发现转化为 MDD 的新疗法仍然很复杂。需要进一步的研究来促进我们对 MDD 病理生理学中涉及线粒体的分子网络和生物学机制的理解。