Department of Anesthesiology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
Research Institute of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, China.
Mil Med Res. 2023 Oct 13;10(1):46. doi: 10.1186/s40779-023-00482-8.
Hypoxic-ischemic injury is a common pathological dysfunction in clinical settings. Mitochondria are sensitive organelles that are readily damaged following ischemia and hypoxia. Dynamin-related protein 1 (Drp1) regulates mitochondrial quality and cellular functions via its oligomeric changes and multiple modifications, which plays a role in mediating the induction of multiple organ damage during hypoxic-ischemic injury. However, there is active controversy and gaps in knowledge regarding the modification, protein interaction, and functions of Drp1, which both hinder and promote development of Drp1 as a novel therapeutic target. Here, we summarize recent findings on the oligomeric changes, modification types, and protein interactions of Drp1 in various hypoxic-ischemic diseases, as well as the Drp1-mediated regulation of mitochondrial quality and cell functions following ischemia and hypoxia. Additionally, potential clinical translation prospects for targeting Drp1 are discussed. This review provides new ideas and targets for proactive interventions on multiple organ damage induced by various hypoxic-ischemic diseases.
缺氧缺血性损伤是临床常见的病理功能障碍。线粒体是对缺血和缺氧敏感的细胞器，容易受到损伤。与动力相关蛋白 1（Drp1）通过其寡聚化变化和多种修饰来调节线粒体质量和细胞功能，在介导缺氧缺血性损伤引起的多器官损伤中发挥作用。然而，关于 Drp1 的修饰、蛋白相互作用和功能存在着活跃的争议和知识空白，这既阻碍了也促进了 Drp1 作为一个新的治疗靶点的发展。在这里，我们总结了 Drp1 在各种缺氧缺血性疾病中的寡聚化变化、修饰类型和蛋白相互作用，以及 Drp1 在缺血缺氧后对线粒体质量和细胞功能的调节作用的最新发现。此外，还讨论了针对 Drp1 的潜在临床转化前景。本综述为针对各种缺氧缺血性疾病引起的多器官损伤的主动干预提供了新的思路和靶点。
