Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Interactomic analysis reveals a new homeostatic role for the HIV restriction factor TRIM5α in mitophagy

Bhaskar Saha, Michelle Salemi, Geneva L Williams, Michael L Paffett, Brett Phinney, View ORCID ProfileMichael A Mandell
doi: https://doi.org/10.1101/2021.08.20.457143
Bhaskar Saha
1Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michelle Salemi
2UC Davis Genome Center, University of California Davis, Davis, CA 95616.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Geneva L Williams
3Biomedical Sciences Graduate Program, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael L Paffett
4Fluorescence Microscopy Shared Resource, University of New Mexico Comprehensive Cancer Center, Albuquerque NM 87131 USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Brett Phinney
2UC Davis Genome Center, University of California Davis, Davis, CA 95616.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael A Mandell
1Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 USA
5Autophagy, Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Michael A Mandell
  • For correspondence: mmandell@salud.unm.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

ABSTRACT

The protein TRIM5α has multiple roles in anti-retroviral defense, but the mechanisms underlying TRIM5α action are unclear. Here, we used an APEX2-based proteomics approach to identify TRIM5α-interacting proteins. Analysis of the TRIM5α interactome found proteins participating in a wide variety of cellular functions including regulating antiviral signaling pathways. We used this data set to uncover a novel role for TRIM5α in mitophagy, an autophagy-based mode of mitochondrial quality control that is compromised in multiple human diseases. Mitochondrial damage triggered the relocalization of TRIM5α to ER-mitochondria contact sites where TRIM5α colocalized with markers of autophagy initiation and autophagosome biogenesis. Furthermore, we found that TRIM5α knockout attenuated both Parkin-dependent and Parkin-independent mitophagy by preventing the recruitment of autophagy regulators FIP200 and ATG13 to unhealthy mitochondria. Finally, TRIM5α knockout cells showed reduced mitochondrial function under basal conditions and were more susceptible to uncontrolled immune activation and cell death in response to mitochondrial damage than were wild type cells. Taken together, our studies have identified a homeostatic role for a protein previously recognized exclusively for its antiviral actions.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted August 20, 2021.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Interactomic analysis reveals a new homeostatic role for the HIV restriction factor TRIM5α in mitophagy
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Interactomic analysis reveals a new homeostatic role for the HIV restriction factor TRIM5α in mitophagy
Bhaskar Saha, Michelle Salemi, Geneva L Williams, Michael L Paffett, Brett Phinney, Michael A Mandell
bioRxiv 2021.08.20.457143; doi: https://doi.org/10.1101/2021.08.20.457143
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Interactomic analysis reveals a new homeostatic role for the HIV restriction factor TRIM5α in mitophagy
Bhaskar Saha, Michelle Salemi, Geneva L Williams, Michael L Paffett, Brett Phinney, Michael A Mandell
bioRxiv 2021.08.20.457143; doi: https://doi.org/10.1101/2021.08.20.457143

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Cell Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4237)
  • Biochemistry (9148)
  • Bioengineering (6788)
  • Bioinformatics (24029)
  • Biophysics (12141)
  • Cancer Biology (9548)
  • Cell Biology (13796)
  • Clinical Trials (138)
  • Developmental Biology (7642)
  • Ecology (11718)
  • Epidemiology (2066)
  • Evolutionary Biology (15519)
  • Genetics (10650)
  • Genomics (14333)
  • Immunology (9493)
  • Microbiology (22858)
  • Molecular Biology (9103)
  • Neuroscience (49034)
  • Paleontology (355)
  • Pathology (1485)
  • Pharmacology and Toxicology (2572)
  • Physiology (3850)
  • Plant Biology (8339)
  • Scientific Communication and Education (1472)
  • Synthetic Biology (2296)
  • Systems Biology (6197)
  • Zoology (1302)