Xu Xieyang, Pang Yan, Fan Xianqun
Department of Ophthalmology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Center for Basic Medical Research and Innovation in Visual System Diseases, Ministry of Education, Shanghai, China.
Signal Transduct Target Ther. 2025 Jun 11;10(1):190. doi: 10.1038/s41392-025-02253-4.
Mitochondria are the energy production centers in cells and have unique genetic information. Due to the irreplaceable function of mitochondria, mitochondrial dysfunction often leads to pathological changes. Mitochondrial dysfunction induces an imbalance between oxidation and antioxidation, mitochondrial DNA (mtDNA) damage, mitochondrial dynamics dysregulation, and changes in mitophagy. It results in oxidative stress due to excessive reactive oxygen species (ROS) generation, which contributes to cell damage and death. Mitochondrial dysfunction can also trigger inflammation through the activation of damage-associated molecular patterns (DAMPs), inflammasomes and inflammatory cells. Besides, mitochondrial alterations in the functional regulation, energy metabolism and genetic stability accompany the aging process, and there has been a lot of evidence suggesting that oxidative stress and inflammation, both of which are associated with mitochondrial dysfunction, are predisposing factors of aging. Therefore, this review hypothesizes that mitochondria serve as central hubs regulating oxidative stress, inflammation, and aging, and their dysfunction contributes to various diseases, including cancers, cardiovascular diseases, neurodegenerative disorders, metabolic diseases, sepsis, ocular pathologies, liver diseases, and autoimmune conditions. Moreover, we outline therapies aimed at various mitochondrial dysfunctions, highlighting their performance in animal models and human trials. Additionally, we focus on the limitations of mitochondrial therapy in clinical applications, and discuss potential future research directions for mitochondrial therapy.
线粒体是细胞中的能量生产中心，具有独特的遗传信息。由于线粒体功能不可替代，线粒体功能障碍常导致病理变化。线粒体功能障碍会导致氧化与抗氧化失衡、线粒体DNA（mtDNA）损伤、线粒体动力学失调以及线粒体自噬改变。它会因活性氧（ROS）生成过多而导致氧化应激，进而造成细胞损伤和死亡。线粒体功能障碍还可通过激活损伤相关分子模式（DAMPs）、炎性小体和炎性细胞引发炎症。此外，线粒体在功能调节、能量代谢和遗传稳定性方面的改变伴随衰老过程，并且有大量证据表明，与线粒体功能障碍相关的氧化应激和炎症是衰老的诱发因素。因此，本综述假设线粒体是调节氧化应激、炎症和衰老的核心枢纽，其功能障碍会导致包括癌症、心血管疾病、神经退行性疾病、代谢疾病、脓毒症、眼部疾病、肝脏疾病和自身免疫性疾病在内的各种疾病。此外，我们概述了针对各种线粒体功能障碍的疗法，重点介绍了它们在动物模型和人体试验中的表现。此外，我们关注线粒体疗法在临床应用中的局限性，并讨论线粒体疗法未来潜在的研究方向。
