Vectorial Import via a Metastable Disulfide-Linked Complex Allows for a Quality Control Step and Import by the Mitochondrial Disulfide Relay.
CHCHD4
Mia40
disulfide formation
disulfide relay
intermembrane space
oxidative folding
proteasome
quality control
vectorial import
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
15 01 2019
15 01 2019
Historique:
received:
15
08
2018
revised:
15
11
2018
accepted:
20
12
2018
entrez:
17
1
2019
pubmed:
17
1
2019
medline:
10
4
2020
Statut:
ppublish
Résumé
Disulfide formation in the mitochondrial intermembrane space (IMS) is an essential process. It is catalyzed by the disulfide relay machinery, which couples substrate import and oxidation. The machinery relies on the oxidoreductase and chaperone CHCHD4-Mia40. Here, we report on the driving force for IMS import and on a redox quality control mechanism. We demonstrate that unfolded reduced proteins, upon translocation into the IMS, initiate formation of a metastable disulfide-linked complex with CHCHD4. If this interaction does not result in productive oxidation, then substrates are released to the cytosol and degraded by the proteasome. Based on these data, we propose a redox quality control step at the level of the disulfide-linked intermediate that relies on the vectorial nature of IMS import. Our findings also provide the mechanistic framework to explain failures in import of numerous human disease mutants in CHCHD4 substrates.
Identifiants
pubmed: 30650365
pii: S2211-1247(18)32052-7
doi: 10.1016/j.celrep.2018.12.092
pii:
doi:
Substances chimiques
Disulfides
0
Mitochondrial Membrane Transport Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
759-774.e5Informations de copyright
Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.