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A protein quality control pathway at the mitochondrial outer membrane

  1. Author:
    Metzger,Meredith [ORCID]
    Scales, Jessica L
    Dunklebarger, Mitchell F
    Loncarek,Jadranka
    Weissman,Allan [ORCID]

  2. Author Address

    Center for Cancer Research, Laboratory of Protein Dynamics and Signaling, National Cancer Institute, Frederick, United States.,
    1. Year: 2020
    2. Date: Mar 02
    3. Epub Date: 2020 03 02
  2. Journal: eLife
    1. 9
  4. Type of Article: Article
  5. Article Number: e51065
  6. ISSN: 2050-084X
  1. Abstract:

    Maintaining the essential functions of mitochondria requires mechanisms to recognize and remove misfolded proteins. However, quality control (QC) pathways for misfolded mitochondrial proteins remain poorly-defined. Here, we establish temperature-sensitive (ts-) peripheral mitochondrial outer membrane (MOM) proteins as novel model QC substrates in Saccharomyces cerevisiae. The ts- proteins sen2-1HAts and sam35-2HAts are degraded from the MOM by the ubiquitin-proteasome system. Ubiquitination of sen2-1HAts is mediated by the ubiquitin ligase (E3) Ubr1, while sam35-2HAts is ubiquitinated primarily by San1. Mitochondria-associated degradation (MAD) of both substrates requires SSA family HSP70s and the HSP40 Sis1, providing the first evidence for chaperone involvement in MAD. In addition to a role for the Cdc48-Npl4-Ufd1 AAA-ATPase complex, Doa1 and a mitochondrial pool of the transmembrane Cdc48 adaptor, Ubx2, are implicated in their degradation. This study reveals a unique QC pathway comprised of a combination of cytosolic and mitochondrial factors that distinguish it from other cellular QC pathways.

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  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.7554/eLife.51065
  3. PMID: 32118579
  4. View record in Web of Science®
  5. WOS: 000524252700001
  6. PII : 51065

Library Notes

  1. Fiscal Year: FY2019-2020
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