期刊
AUTOPHAGY
卷 -, 期 -, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2022.2052460
关键词
Endosomes; mitophagy; PRKN; RFFL; ubiquitin ligases
类别
资金
- DST-INSPIRE
- DBT
- IISER TVM
- Department of Biotechnology [BT/PR21325/BRB/10/1554/2016]
- Department of Science and Technology-Science and Engineering Research Board (DST-SERB) grant [EMR/2016/008048, IPA/2020/000070]
This study reveals a novel role of endosomes in modulating upstream pathways of PRKN-dependent mitophagy initiation.
Mutations in the ubiquitin ligase PRKN (parkin RBR E3 ubiquitin protein ligase) are associated with Parkinson disease and defective mitophagy. Conceptually, PRKN-dependent mitophagy is classified into two phases: 1. PRKN recruits to and ubiquitinates mitochondrial proteins; 2. formation of phagophore membrane, sequestering mitochondria for degradation. Recently, endosomal machineries are reported to contribute to the later stage for membrane assembly. We reported a role for endosomes in the events upstream of phase 1. We demonstrate that the endosomal ubiquitin ligase RFFL (ring finger and FYVE like domain containing E3 ubiquitin protein ligase) associated with damaged mitochondria, and this association preceded that of PRKN. RFFL interacted with PRKN, and stable recruitment of PRKN to damaged mitochondria was substantially reduced in RFFL KO cells. Our study unraveled a novel role of endosomes in modulating upstream pathways of PRKN-dependent mitophagy initiation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据