Endosomes facilitate mitochondrial clearance by enhancing Parkin recruitment to mitochondria
Year: 2020
Type: preprint
Abstract: Mutations in ubiquitin ligase Parkin are associated with Parkinson’s disease and defective mitophagy. Conceptually, Parkin-dependent mitophagy is classified into two phases; 1. Parkin recruits to and ubiquitinates mitochondrial proteins, 2. Formation of autophagosome membrane, sequestering mitochondria for degradation. Recently, endosomal machineries were reported to contribute to the later stage for membrane assembly. We report a role for endosomes in the events upstream of phase 1. We demonstrate that an endosomal ubiquitin ligase CARP2 associates with damaged mitochondria, and this association precedes that of Parkin. CARP2 interacts with Parkin, and stable recruitment of Parkin to damaged mitochondria was substantially reduced in CARP2 KO cells. Our study unravels a novel role of endosomes in modulating upstream pathways of Parkin-dependent mitophagy initiation.
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Indian Institute of Science Education and Research Thiruvananthapuram, Department of Biotechnology, Ministry of Science and Technology, India, Department of Science and Technology, Ministry of Science and Technology, India, Indian Institute of Science Education and Research Mohali, Science and Engineering Research Board
Awards: G5238168788, G8572416517, G8797283278
OpenAlex ID: W3007805507