Dataset Information

SNX10 regulates the clearance of mitochondrial proteins and mitochondrial bioenergetics

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. SNX10-positive vesicles contain COX-IV and SAMM50, both proteins being important for mitochondrial respiratory chain function, while other mitochondrial proteins are excluded. We find that depletion of SNX10 results in lower levels of COX-IV and SAMM50 both in vitro and in a zebrafish model, as well as impaired mitochondrial respiration and reduced citrate synthase activity, indicating a role for SNX10 as a regulator of mitochondrial bioenergetics. Importantly, the knockout of SNX10 homologs in zebrafish led to elevated ROS levels and cell death, demonstrating the in vivo relevance of SNX10-mediated regulation of mitochondrial homeostasis.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Sachin Singh

LAB HEAD: Tuula Anneli Nyman

PROVIDER: PXD056720 | Pride | 2025-05-07

REPOSITORIES: Pride

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SNX10 functions as a modulator of piecemeal mitophagy and mitochondrial bioenergetics.

Trachsel-Moncho Laura L Veroni Chiara C Mathai Benan John BJ Lapao Ana A Singh Sakshi S Asp Nagham Theres NT Schultz Sebastian W SW Pankiv Serhiy S Simonsen Anne A

The Journal of cell biology 20250307 5

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. Upon hypoxia-mimicking conditions, SNX10 localizes to late endosomal structures containing selected mitochondrial proteins, including COX-IV and SAMM50, and the autophagy proteins SQST ...[more]

PMID: 40052924

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