Show simple item record

dc.contributor.authorMetzger, Meredith B
dc.contributor.authorScales, Jessica L
dc.contributor.authorDunklebarger, Mitchell F
dc.contributor.authorLoncarek, Jadranka
dc.contributor.authorWeissman, Allan M
dc.date.accessioned2020-04-07T01:08:33Z
dc.date.available2020-04-07T01:08:33Z
dc.date.issued2020-03-02
dc.date.submitted2019-08-14
dc.identifier.issn2050-084X
dc.identifier.other51065
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/304170
dc.description.abstractMaintaining 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 the SSA family of 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.
dc.languageen
dc.publishereLife Sciences Publications, Ltd
dc.rightsCC0 1.0 Universal (CC0 1.0) Public Domain Dedication
dc.rights.urihttps://creativecommons.org/publicdomain/zero/1.0/
dc.subjectResearch Article
dc.subjectCell Biology
dc.subjectUPS
dc.subjectquality control
dc.subjectyeast
dc.subjectmisfolded
dc.subjectMAD
dc.subjectS. cerevisiae
dc.titleA protein quality control pathway at the mitochondrial outer membrane.
dc.typeArticle
dc.date.updated2020-04-07T01:08:32Z
prism.publicationNameElife
prism.volume9
dc.identifier.doi10.17863/CAM.51255
dcterms.dateAccepted2020-03-01
rioxxterms.versionofrecord10.7554/eLife.51065
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/publicdomain/zero/1.0/
datacite.contributor.supervisorsenior_editor: Ron, David
datacite.contributor.supervisoreditor: Chacinska, Agnieszka
dc.contributor.orcidMetzger, Meredith B [0000-0002-6248-0009]
dc.contributor.orcidWeissman, Allan M [0000-0002-7865-7702]
dc.identifier.eissn2050-084X
pubs.funder-project-idNational Cancer Institute (Intramural Research Program)
cam.issuedOnline2020-03-02


Files in this item

Thumbnail
Thumbnail
Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record

CC0 1.0 Universal (CC0 1.0) Public Domain Dedication
Except where otherwise noted, this item's licence is described as CC0 1.0 Universal (CC0 1.0) Public Domain Dedication