AIFM1 is a component of the mitochondrial disulfide relay that drives complex I assembly through efficient import of NDUFS5.
Apoptosis Inducing Factor
/ metabolism
Disulfides
/ metabolism
Electron Transport Complex I
/ metabolism
HEK293 Cells
Humans
Mitochondrial Membrane Transport Proteins
/ genetics
Mitochondrial Precursor Protein Import Complex Proteins
Mitochondrial Proteins
/ genetics
Oxidation-Reduction
Protein Transport
AIFM1
MIA40-CHCHD4
NDUFS5
complex I
mitochondrial disulfide relay
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
01 09 2022
01 09 2022
Historique:
revised:
26
06
2022
received:
27
01
2022
accepted:
30
06
2022
pubmed:
22
7
2022
medline:
9
9
2022
entrez:
21
7
2022
Statut:
ppublish
Résumé
The mitochondrial intermembrane space protein AIFM1 has been reported to mediate the import of MIA40/CHCHD4, which forms the import receptor in the mitochondrial disulfide relay. Here, we demonstrate that AIFM1 and MIA40/CHCHD4 cooperate beyond this MIA40/CHCHD4 import. We show that AIFM1 and MIA40/CHCHD4 form a stable long-lived complex in vitro, in different cell lines, and in tissues. In HEK293 cells lacking AIFM1, levels of MIA40 are unchanged, but the protein is present in the monomeric form. Monomeric MIA40 neither efficiently interacts with nor mediates the import of specific substrates. The import defect is especially severe for NDUFS5, a subunit of complex I of the respiratory chain. As a consequence, NDUFS5 accumulates in the cytosol and undergoes rapid proteasomal degradation. Lack of mitochondrial NDUFS5 in turn results in stalling of complex I assembly. Collectively, we demonstrate that AIFM1 serves two overlapping functions: importing MIA40/CHCHD4 and constituting an integral part of the disulfide relay that ensures efficient interaction of MIA40/CHCHD4 with specific substrates.
Identifiants
pubmed: 35859387
doi: 10.15252/embj.2022110784
pmc: PMC9434101
doi:
Substances chimiques
AIFM1 protein, human
0
Apoptosis Inducing Factor
0
Disulfides
0
Mitochondrial Membrane Transport Proteins
0
Mitochondrial Precursor Protein Import Complex Proteins
0
Mitochondrial Proteins
0
NDUFS5 protein, human
0
Electron Transport Complex I
EC 7.1.1.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e110784Informations de copyright
© 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.
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