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Cited by 16Autophagy in Disease and TherapyCellular transport and secretionMitochondrial Function and Pathology

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SNX10 functions as a modulator of piecemeal mitophagy and mitochondrial bioenergetics

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Trachsel-Moncho, Laura, Veroni, Chiara, Mathai, Benan John, Lapao, Ana, Singh, Sakshi, Asp, Nagham Theres, Schultz, Sebastian W., Pankiv, Serhiy, Simonsen, Anne·2025·Journal of Cell Biology
DOI 10.1083/jcb.202404009PMC PMC11893173

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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. Upon hypoxia-mimicking conditions, SNX10 localizes to late endosomal structures containing selected mitochondrial proteins, including COX-IV and SAMM50, and the autophagy proteins SQSTM1/p62 and LC3B. The turnover of COX-IV was enhanced in SNX10-depleted cells, with a corresponding reduced mitochondrial respiration and citrate synthase activity. Importantly, zebrafish larvae lacking Snx10 show reduced levels of Cox-IV, as well as elevated ROS levels and ROS-mediated cell death in the brain, demonstrating the in vivo relevance of SNX10-mediated modulation of mitochondrial bioenergetics.

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Metadata

Authors
Trachsel-Moncho, L., Veroni, C., Mathai, B. J., Lapao, A., Singh, S., Asp, N. T., Schultz, S. W., Pankiv, S., & Simonsen, A.
Affiliations
  • Oslo University Hospital (NO)
  • University of Oslo 1 Department of Molecular Medicine, Institute of Basic Medical Sciences Faculty of Medicine, , Oslo,
  • University of Oslo (NO)
Corresponding author
Simonsen, Anne
ORCID
Venue
Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2025-03-07
Volume
224
Issue
5
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.202404009
PMC
PMC11893173
OpenAlex
W4408245104
Cited by
16
References
1
Citations by year
2026: 13 · 2025: 3
FWCI
11.09
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of Cell Biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • University of Oslo
  • South-Eastern Norway Regional Health Authority (2020032)
  • Research Council of Norway (295910, 262652, 249753)
  • Norwegian Cancer Society (171318, 223278)
  • Marie Skłodowska-Curie (801133)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords
SNX10, mitochondrial bioenergetics, phosphatidylinositol 3-phosphate, endosomal trafficking, late endosomes, cytochrome c oxidase subunit IV, SAMM50, p62, LC3B, mitochondrial respiration, citrate synthase, reactive oxygen species, zebrafish brain, hypoxia
MeSH terms
Animals, Electron Transport Complex IV, Energy Metabolism, HeLa Cells, Humans, Mitochondria, Oxidative Phosphorylation, Endosomes, Zebrafish, Reactive Oxygen Species, Mitochondrial Proteins, Zebrafish Proteins, Sorting Nexins, Mitophagy

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