Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York-Presbyterian Hospital/Weill Cornell Medical Center, Weill Cornell Medicine, New York, New York, United States.
Proterris Inc., Boston, Massachusetts, United States.
Physiol Rev. 2023 Oct 1;103(4):2349-2422. doi: 10.1152/physrev.00058.2021. Epub 2023 Apr 6.
Mitochondria are well known as organelles responsible for the maintenance of cellular bioenergetics through the production of ATP. Although oxidative phosphorylation may be their most important function, mitochondria are also integral for the synthesis of metabolic precursors, calcium regulation, the production of reactive oxygen species, immune signaling, and apoptosis. Considering the breadth of their responsibilities, mitochondria are fundamental for cellular metabolism and homeostasis. Appreciating this significance, translational medicine has begun to investigate how mitochondrial dysfunction can represent a harbinger of disease. In this review, we provide a detailed overview of mitochondrial metabolism, cellular bioenergetics, mitochondrial dynamics, autophagy, mitochondrial damage-associated molecular patterns, mitochondria-mediated cell death pathways, and how mitochondrial dysfunction at any of these levels is associated with disease pathogenesis. Mitochondria-dependent pathways may thereby represent an attractive therapeutic target for ameliorating human disease.
线粒体是众所周知的细胞器,通过产生 ATP 来维持细胞的生物能量。尽管氧化磷酸化可能是它们最重要的功能,但线粒体对于代谢前体的合成、钙调节、活性氧的产生、免疫信号和细胞凋亡也是必不可少的。考虑到它们的职责广泛,线粒体对于细胞代谢和内稳态至关重要。认识到这一重要性,转化医学已经开始研究线粒体功能障碍如何预示疾病。在这篇综述中,我们详细概述了线粒体代谢、细胞生物能量学、线粒体动力学、自噬、线粒体损伤相关分子模式、线粒体介导的细胞死亡途径,以及这些水平上的任何线粒体功能障碍如何与疾病发病机制相关。因此,线粒体依赖性途径可能代表改善人类疾病的有吸引力的治疗靶点。