Benan John Mathai

Abstract We here identify the endosomal protein SNX10 as a negative regulator of piecemeal mitophagy of OXPHOS machinery components. In control conditions, SNX10 localizes to early endocytic compartments in a PtdIns3P-dependent manner and modulates endosomal trafficking but also shows dynamic connections with mitochondria.

Abstract We here show that SNX10 localizes to endocytic compartments in a PtdIns3P-dependent manner and that mutations in the PX domain associated with autosomal recessive osteopetrosis prevent its endosomal recruitment. We demonstrate that SNX10 regulates endosomal trafficking but also interacts with mitochondrial proteins and shows dynamic interactions with mitochondria. Intriguingly, SNX10 and RAB5A-positive vesicles contain mitochondrial material and stain positive for LC3B.

Highlights • The mitochondria proteins NIPSNAP1 and NIPSNAP2 bind to autophagy-related proteins • NIPSNAP1 and NIPSNAP2 recruit autophagy receptors to depolarized mitochondria • NIPSNAP1 and NIPSNAP2, acting redundantly, are required for PARKIN-dependent mitophagy • Nipsnap1-deficient zebrafish larvae display parkinsonism Summary The clearance of damaged or dysfunctional mitochondria by selective autophagy (mitophagy) is important for cellular homeostasis and prevention of disease.