Mitochondria are responsible for providing our cells with energy, as well as regulating oxidative stress and apoptosis, and considerable evidence demonstrates that mitochondria-related alterations are prevalent during chronic stress and depression. Here, we discuss how chronic stress may induce depressive behavior by potentiating mitochondrial allostatic load, which ultimately decreases energy production, elevates the generation of harmful reactive oxygen species, damages mitochondrial DNA and increases membrane permeability and pro-apoptotic factor release. We also discuss how mitochondrial insults can exacerbate the immune response, contributing to depressive symptomology. Furthermore, we illustrate how depression symptoms are associated with specific mitochondrial defects, and how targeting of these defects with pharmacological agents may be a promising avenue for the development of novel, more efficacious antidepressants. In summary, this review supports the notion that severe psychosocial stress induces mitochondrial dysfunction, thereby increasing the vulnerability to developing depressive symptoms.

中文翻译：

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严重的生活压力、线粒体功能障碍和抑郁行为：病理生理学和治疗观点

线粒体负责为我们的细胞提供能量，以及调节氧化应激和细胞凋亡，大量证据表明，线粒体相关的改变在慢性应激和抑郁期间普遍存在。在这里，我们讨论了慢性压力如何通过增强线粒体平衡负荷来诱导抑郁行为，最终减少能量产生，增加有害活性氧的产生，破坏线粒体 DNA，增加膜通透性和促凋亡因子释放。我们还讨论了线粒体损伤如何加剧免疫反应，导致抑郁症状。此外，我们说明了抑郁症状如何与特定的线粒体缺陷相关，以及如何用药物靶向这些缺陷可能是开发新型、更有效的抗抑郁药的有希望的途径。总之，本综述支持严重的社会心理压力会导致线粒体功能障碍，从而增加出现抑郁症状的脆弱性的观点。