Interactomic analysis reveals a homeostatic role for the HIV restriction factor TRIM5α in mitophagy
| Autor: | Bhaskar Saha, Michelle Salemi, Geneva L. Williams, Seeun Oh, Michael L. Paffett, Brett Phinney, Michael A. Mandell |
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| Rok vydání: | 2022 |
| Předmět: |
APEX2
autophagy mitochondrial metabolism Ubiquitin-Protein Ligases 1.1 Normal biological development and functioning Medical Physiology HIV Infections General Biochemistry Genetics and Molecular Biology tripartite motif Tripartite Motif Proteins Antiviral Restriction Factors proteomics TRIM5α ER-mitochondria contact site Underpinning research Autophagy Humans 2.1 Biological and endogenous factors Aetiology Mitophagy HIV Proteins Cell biology [CP] ULK1 complex Infectious Diseases inflammation HIV-1 Immunology [CP] Biochemistry and Cell Biology |
| Zdroj: | Cell reports, vol 39, iss 6 |
| Popis: | The protein TRIM5α has multiple roles in antiretroviral defense, but the mechanisms underlying TRIM5α action are unclear. Here, we employ APEX2-based proteomics to identify TRIM5α-interacting partners. Our proteomics results connect TRIM5 to other proteins with actions in antiviral defense. Additionally, they link TRIM5 to mitophagy, an autophagy-based mode of mitochondrial quality control that is compromised in several human diseases. We find that TRIM5 is required for Parkin-dependent and -independent mitophagy pathways where TRIM5 recruits upstream autophagy regulators to damaged mitochondria. Expression of a TRIM5 mutant lacking ubiquitin ligase activity is unable to rescue mitophagy in TRIM5 knockout cells. Cells lacking TRIM5 show reduced mitochondrial function under basal conditions and are more susceptible to immune activation and death in response to mitochondrial damage than are wild-type cells. Taken together, our studies identify a homeostatic role for a protein previously recognized exclusively for its antiviral actions. |
| Databáze: | OpenAIRE |
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