Peroxiredoxin 6 Is a Crucial Factor in the Initial Step of Mitochondrial   Clearance and Is Upstream of the PINK1-Parkin Pathway

doi:10.1089/ars.2015.6336

CORC > 北京大学 > 生命科学学院

	Peroxiredoxin 6 Is a Crucial Factor in the Initial Step of Mitochondrial Clearance and Is Upstream of the PINK1-Parkin Pathway
	Ma, Shuaipeng ; Zhang, Xuefei ; Zheng, Liangjun ; Li, Zeyang ; Zhao, Xuyang ; Lai, Wenjia ; Shen, Hongyan ; Lv, Junniao ; Yang, Guofeng ; Wang, Qingsong ; Ji, Jianguo
刊名	ANTIOXIDANTS & REDOX SIGNALING
	2016
关键词	SPECTROMETRY-BASED PROTEOMICS LENS EPITHELIAL-CELLS PARKINSONS-DISEASE OXIDATIVE-STRESS ALZHEIMERS-DISEASE GLUTATHIONE-PEROXIDASE ENRICHMENT ANALYSIS MOUSE MODEL HUMAN BRAIN AD MODELS
DOI	10.1089/ars.2015.6336
英文摘要	Aims: PTEN-putative kinase 1 (PINK1)-Parkin-mediated mitophagy is crucial for the clearance of damaged mitochondria. However, the mechanisms underlying PINK1-Parkin-mediated mitophagy are not fully understood. The goal of this study is to identify new regulators and to elucidate the regulatory mechanisms of mitophagy. Results: Quantitative mitochondrial proteomic analysis revealed that 63 proteins showed increased levels and 36 proteins showed decreased levels in cells subjected to carbonyl cyanide m-chlorophenyl hydrazone (CCCP) treatment. Peroxiredoxin 6 (PRDX6 or Prx6), a unique member of the ubiquitous PRDX family, was recruited to depolarized mitochondria. Reactive oxygen species (ROS) generated by CCCP promoted PRDX6 accumulation and PINK1 stabilization in damaged mitochondria and induced mitophagy. In addition, depletion of PRDX6 resulted in the stabilization of PINK1, accumulation of autophagic marker, p62, translocation of Parkin to mitochondria, and lipidation of microtubule-associated protein 1 light chain 3. Furthermore, these events were blocked upon supplementation with antioxidant N-acetyl-l-cysteine or depletion of PINK1. Innovation: This is the first study to demonstrate that PRDX6 is the only member of the PRDX family that relocates to damaged mitochondria, where it plays a crucial role in the initial stage of mitophagy by controlling ROS homeostasis. Conclusion: ROS induce the recruitment of PRDX6 to mitochondria, where PRDX6 controls ROS homeostasis in the initial step of PINK1-Parkin-mediated mitophagy. Our study provides new insight into the initial regulatory mechanisms of mitophagy and reveals the protective role of PRDX6 in the clearance of damaged mitochondria. Antioxid. Redox Signal. 24, 486-501.; National Natural Science Foundation of China [31270872, 31470807, 31200610]; National Key Basic Research Program of China [2010CB912203, 2011CB915504]; Beijing Natural Science Foundation [5142010]; SCI(E); PubMed; ARTICLE; yang-guofeng@163.com; wangqingsong@pku.edu.cn; jijg@pku.edu.cn; 9; 486-501; 24
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/416847]
专题	生命科学学院
推荐引用方式 GB/T 7714	Ma, Shuaipeng,Zhang, Xuefei,Zheng, Liangjun,et al. Peroxiredoxin 6 Is a Crucial Factor in the Initial Step of Mitochondrial Clearance and Is Upstream of the PINK1-Parkin Pathway[J]. ANTIOXIDANTS & REDOX SIGNALING,2016.
APA	Ma, Shuaipeng.,Zhang, Xuefei.,Zheng, Liangjun.,Li, Zeyang.,Zhao, Xuyang.,...&Ji, Jianguo.(2016).Peroxiredoxin 6 Is a Crucial Factor in the Initial Step of Mitochondrial Clearance and Is Upstream of the PINK1-Parkin Pathway.ANTIOXIDANTS & REDOX SIGNALING.
MLA	Ma, Shuaipeng,et al."Peroxiredoxin 6 Is a Crucial Factor in the Initial Step of Mitochondrial Clearance and Is Upstream of the PINK1-Parkin Pathway".ANTIOXIDANTS & REDOX SIGNALING (2016).