Feb 19, 2020

Endosomes facilitate mitochondrial clearance by enhancing Mfn2 degradation and subsequent Parkin recruitment

bioRxiv
Rishith RavindranSrinivasa M Srinivasula

Abstract

Mitochondrial quality control and homeostasis is ensured by removal of the damaged mitochondria involving lysosomal and proteasomal degradation mechanisms. Though much remains to be elucidated, recent findings suggest important roles for endosomal machinery in the elimination of damaged mitochondria. In this study, we report a novel function for a FYVE-like domain containing endosomal ubiquitin ligase, CARP2 in mitophagy. Our results show that endosomal CARP2 associates with damaged mitochondria, and this association precedes that of Parkin, whose recruitment is known to be essential for mitochondrial clearance. Association of Parkin to damaged mitochondria was substantially reduced in CARP2 KO cells upon CCCP treatment. We also demonstrate that Mitofusin-2 degradation, which is a prerequisite for Parkin recruitment during damage, was inhibited in CARP2-deficient cells. Hence, we conclude that endosomal-associated CARP2 facilitates mitophagy by regulating Parkin recruitment and activation by targeting Mitofusin-2. Our study proposes a model on how heterogenous endocytic machinery can interact with damaged mitochondria and unravel a new mechanism for mitochondrial clearance.

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Mentioned in this Paper

Finding
Mitochondrial Degradation
Endocytosis
Mitochondrial Inheritance
CA11 gene
MFN2 protein, human
Endosomes
Mitochondria
Study
PARK 2 protein, human

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