Endosomal RFFL ubiquitin ligase regulates mitochondrial morphology by targeting mitofusin 2.

ABSTRACT: Mitochondrial homeostasis is ensured through communication between diverse cellular organelles, including mitochondria, the endoplasmic reticulum (ER), lysosomes and endosomes. Although it is known that mitofusins regulate mitochondrial networks and ER contacts, their role in endosomal-mitochondrial interactions remains unclear. Previously, we have reported that vesicles positive for the endosomal ubiquitin ligase RFFL are associated with damaged mitochondria and prime the organelle for PRKN recruitment. Now, we establish that RFFL is a ubiquitin ligase for mitofusin 2 (MFN2). Using electron microscopy and confocal imaging analyses, we demonstrate that RFFL-knockout cells exhibit enlarged mitochondrial morphology. RFFL interacts at an endogenous level with MFN2 and contributes to its ubiqu

SUBMITTER: Narendradev ND 

PROVIDER: S-EPMC12211564 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature