Dependence of PINK1 accumulation on mitochondrial redox system.,Aging Cell

当前位置： X-MOL 学术 › Aging Cell › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Dependence of PINK1 accumulation on mitochondrial redox system.
Aging Cell ( IF 8.0 ) Pub Date : 2020-08-11 , DOI: 10.1111/acel.13211
Feng Gao _{1,

2} , Yan Zhang ₁ , Xiaoou Hou ₁ , Zhouteng Tao _{1,

3} , Haigang Ren ₁ , Guanghui Wang ₁

Affiliation

Accumulation of PINK1 on the outer mitochondrial membrane (OMM) is necessary for PINK‐mediated mitophagy. The proton ionophores, like carbonyl cyanide m‐chlorophenylhydrazone (CCCP) and carbonyl cyanide‐4‐(trifluoromethoxy)phenylhydrazone (FCCP), inhibit PINK1 import into mitochondrial matrix and induce PINK1 OMM accumulation. Here, we show that the CHCHD4/GFER disulfide relay system in the mitochondrial intermembrane space (IMS) is required for PINK1 stabilization when mitochondrial membrane potential is lost. Activation of CHCHD4/GFER system by mitochondrial oxidative stress or inhibition of CHCHD4/GFER system with antioxidants can promote or suppress PINK1 accumulation, respectively. Thus data suggest a pivotal role of CHCHD4/GFER system in PINK1 accumulation. The amyotrophic lateral sclerosis‐related superoxide dismutase 1 mutants dysregulated redox state and CHCHD4/GFER system in the IMS, leading to inhibitions of PINK1 accumulation and mitophagy. Thus, the redox system in the IMS is involved in PINK1 accumulation and damaged mitochondrial clearance, which may play roles in mitochondrial dysfunction‐related neurodegenerative diseases.

中文翻译：

PINK1 积累对线粒体氧化还原系统的依赖性。

PINK1 在线粒体外膜 (OMM) 上的积累是 PINK 介导的线粒体自噬所必需的。质子离子载体，如羰基氰化物间氯苯腙（CCCP）和羰基氰化物-4-（三氟甲氧基）苯腙（FCCP），抑制 PINK1 进入线粒体基质并诱导 PINK1 OMM 积累。在这里，我们表明当线粒体膜电位丢失时，线粒体膜间隙（IMS）中的 CHCHD4/GFER 二硫化物中继系统是 PINK1 稳定所必需的。线粒体氧化应激激活 CHCHD4/GFER 系统或用抗氧化剂抑制 CHCHD4/GFER 系统可分别促进或抑制 PINK1 的积累。因此，数据表明 CHCHD4/GFER 系统在 PINK1 积累中的关键作用。肌萎缩侧索硬化相关的超氧化物歧化酶 1 突变体在 IMS 中失调氧化还原状态和 CHCHD4/GFER 系统，导致抑制 PINK1 积累和线粒体自噬。因此，IMS中的氧化还原系统参与PINK1积累和线粒体清除受损，这可能在线粒体功能障碍相关的神经退行性疾病中发挥作用。

更新日期：2020-09-24

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11