Back to Search Start Over

Endosomes facilitate mitochondrial clearance by enhancing Parkin recruitment to mitochondria

Authors :
Aneesh Chandrasekharan
Nikhil Dev Narendradev
T.R. Santhoshkumar
Rishith Ravindran
Anoop Kumar G. Velikkakath
Srinivasa M. Srinivasula
Publication Year :
2020
Publisher :
Cold Spring Harbor Laboratory, 2020.

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.

Details

Database :
OpenAIRE
Accession number :
edsair.doi...........0849de48ce4e5afa334e2d5ff95c3a43
Full Text :
https://doi.org/10.1101/2020.02.19.955880