The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan City People's Hospital, Qingyuan, Guangdong, China.
Xiangya Hospital, Central South University, Changsha, Hunan, China.
Signal Transduct Target Ther. 2023 Aug 16;8(1):304. doi: 10.1038/s41392-023-01503-7.
Mitochondria are dynamic organelles with multiple functions. They participate in necrotic cell death and programmed apoptotic, and are crucial for cell metabolism and survival. Mitophagy serves as a cytoprotective mechanism to remove superfluous or dysfunctional mitochondria and maintain mitochondrial fine-tuning numbers to balance intracellular homeostasis. Growing evidences show that mitophagy, as an acute tissue stress response, plays an important role in maintaining the health of the mitochondrial network. Since the timely removal of abnormal mitochondria is essential for cell survival, cells have evolved a variety of mitophagy pathways to ensure that mitophagy can be activated in time under various environments. A better understanding of the mechanism of mitophagy in various diseases is crucial for the treatment of diseases and therapeutic target design. In this review, we summarize the molecular mechanisms of mitophagy-mediated mitochondrial elimination, how mitophagy maintains mitochondrial homeostasis at the system levels and organ, and what alterations in mitophagy are related to the development of diseases, including neurological, cardiovascular, pulmonary, hepatic, renal disease, etc., in recent advances. Finally, we summarize the potential clinical applications and outline the conditions for mitophagy regulators to enter clinical trials. Research advances in signaling transduction of mitophagy will have an important role in developing new therapeutic strategies for precision medicine.
线粒体是具有多种功能的动态细胞器。它们参与坏死性细胞死亡和程序性细胞凋亡，对细胞代谢和存活至关重要。线粒体自噬作为一种细胞保护机制，可清除多余或功能失调的线粒体，并维持线粒体的精细调节数量以平衡细胞内的动态平衡。越来越多的证据表明，线粒体自噬作为一种急性组织应激反应，在维持线粒体网络的健康方面发挥着重要作用。由于及时清除异常线粒体对于细胞存活至关重要，因此细胞已经进化出多种线粒体自噬途径，以确保在各种环境下及时激活线粒体自噬。更好地了解各种疾病中线粒体自噬的机制对于疾病的治疗和治疗靶点的设计至关重要。在这篇综述中，我们总结了线粒体自噬介导的线粒体消除的分子机制，线粒体自噬如何在系统和器官水平维持线粒体的动态平衡，以及线粒体自噬的改变与疾病的发展有何关系，包括神经、心血管、肺部、肝脏、肾脏疾病等。最后，我们总结了线粒体自噬调节剂进入临床试验的潜在临床应用和条件。线粒体自噬信号转导的研究进展将在开发精准医学的新治疗策略方面发挥重要作用。
