Parkin调控凋亡、坏死性凋亡和焦亡的研究进展

Research Progress on Parkin in Regulating Apoptosis,Necroptosis and Pyroptosis

细胞的死亡有多种形式,包括凋亡、坏死性凋亡、焦亡等,各具有独特的分子特征,发挥着不同的功能。近年来,对各种死亡形式的功能和机制研究不断深入,围绕着细胞死亡途径的特征分子及其调控取得重要进展。Parkin作为E3泛素连接酶,通过其对底物的泛素化修饰,而发挥多种生物学功能。除了其被熟知的介导线粒体自噬途径之外,近年的研究还发现Parkin通过直接泛素化修饰多种"死亡"特征分子调控细胞死亡进程和肿瘤的发生。该文综述了Parkin参与调控细胞死亡进程的作用和方式,对其以线粒体自噬依赖和非依赖的方式调控细胞死亡的机制深度解析,以揭示细胞死亡相关的分子生物学奥秘。

There exist multiple cell death pathways,including apoptosis,necroptosis and pyroptosis,which are defined by different signaling and execution pathways,and play disparate roles in a wide range of cellular processes.The functions and mechanisms of cell death have been intensively studied in recent years,and a great progress has been made toward understanding the molecular machinery of cell death pathways.Parkin,an E3 ubiquitin ligase,exhibits a plethora of biological activities in various cellular processes by ubiquitination of its specific substrates.In addition to its well-characterized activities in mediating mitophagy,recent studies also highlight its roles in regulating cell death pathways and pathogenesis of cancer via direct ubiquitination of several characteristic“death”substrates.This review summarizes the recent advance in the role and the action mechanism of Parkin in cell death pathways with a focus on apoptosis,necroptosis and pyroptosis,which provides in-depth comprehension of mitophagy-dependent,as well as independent,revealing the biological mystery associated with cell death.