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TANK结合激酶1在PINK1/Parkin依赖性和非依赖性线粒体自噬中的作用研究进展

邓豪¹, 夏志^2,3, 尚画雨^2,*

¹成都体育学院运动医学与健康学院，成都 610041；²温州大学体育与健康学院，温州 325035；³井冈山大学体育学院，吉安 343009

摘要

线粒体自噬是一种清除受损或多余线粒体的过程，在调节细胞内线粒体质量和维持线粒体能量代谢等方面发挥重要作用。TANK结合激酶1 (TANK-binding kinase 1, TBK1)是一种多功能的丝氨酸/苏氨酸蛋白激酶，同时参与调控PTEN诱导假定激酶1 (PTEN-induced putative kinase 1, PINK1)/Parkin依赖性和非依赖性线粒体自噬过程。近期研究表明，TBK1可磷酸化视神经蛋白(optineurin, OPTN)、p62/sequestosome-1、Ras相关GTP结合蛋白7 (Ras-related GTP binding protein 7, Rab7)等自噬相关蛋白，并介导核点蛋白52 (nuclear dot protein 52, NDP52)与UNC-51样自噬激活激酶1 (UNC-51 like autophagy activating kinase 1, ULK1)复合物相结合，以及TAX1结合蛋白1 (TAX1-binding protein 1, TAX1BP1)与微管相关蛋白1轻链3 (microtubule- associated protein 1 light chain 3, LC3)相结合，从而增强PINK1/Parkin依赖性线粒体自噬。TBK1亦可作为AMP活化蛋白激酶(AMP-activated protein kinase, AMPK)/ULK1自噬通路的作用底物而被激活，再通过磷酸化动力相关蛋白1 (dynamin-related protein 1, Drp1)、Rab7促进PINK1/Parkin非依赖性线粒体自噬。本文对TBK1在PINK1/Parkin依赖性和非依赖性线粒体自噬中的作用及机制进行了综述。

关键词： 线粒体; 线粒体自噬; TANK结合激酶1; PTEN诱导假定激酶1; Parkin

Research progress on the role of TANK-binding kinase 1 in PINK1/Parkin- dependent and -independent mitophagy

DENG Hao¹, XIA Zhi^2,3, SHANG Hua-Yu^2,*

¹School of Sports Medicine and Health, Chengdu Sport University, Chengdu 610041, China；²College of Physical Education and Health, Wenzhou University, Wenzhou 325035, China；³Physical Education College of Jinggangshan University, Ji’an 343009, China

Abstract

Mitophagy is a process that selectively removes excess or damaged mitochondria and plays an important role in regulating intracellular mitochondrial mass and maintaining mitochondrial energy metabolism. TANK-binding kinase 1 (TBK1) is a multifunctional serine/threonine protein kinase, which is involved in the regulation of PTEN-induced putative kinase 1 (PINK1)/Parkin-dependent and -independent mitophagy. Recent studies have shown that TBK1 phosphorylates the autophagy related proteins, such as optineurin (OPTN), p62/sequestosome-1, Ras-related GTP binding protein 7 (Rab7), and mediates the binding of nuclear dot protein 52 (NDP52) to UNC-51 like autophagy activating kinase 1 (ULK1) complex, as well as the binding of TAX1-binding protein 1 (TAX1BP1) to microtubule-associated protein 1 light chain 3 (LC3), thereby enhancing PINK1/Parkin-dependent mitophagy. In addition, TBK1 is a direct substrate of AMP-activated protein kinase (AMPK)/ULK1 pathway, and its activation phosphorylates dynamin-related protein 1 (Drp1) and Rab7 to promote PINK1/Parkin-independent mitophagy. This article reviews the role and mechanism of TBK1 in regulating PINK1/Parkin-dependent and -independent mitophagy.

Key words: mitochondrion; mitophagy; TANK-binding kinase 1; PTEN-induced putative kinase 1; Parkin

收稿日期：　　录用日期：

通讯作者：尚画雨　　E-mail: santanasan@163.com

DOI: 10.13294/j.aps.2023.0061

引用本文：

邓豪, 夏志, 尚画雨. TANK结合激酶1在PINK1/Parkin依赖性和非依赖性线粒体自噬中的作用研究进展[J]. 生理学报 2024; 76 (1): 161-172.

DENG Hao, XIA Zhi, SHANG Hua-Yu. Research progress on the role of TANK-binding kinase 1 in PINK1/Parkin- dependent and -independent mitophagy. Acta Physiol Sin 2024; 76 (1): 161-172 (in Chinese with English abstract).