Homozygous missense mutation in UQCRC2 associated with severe encephalomyopathy, mitochondrial complex III assembly defect and activation of mitochondrial protein quality control.
Caseinolytic mitochondrial matrix peptidase proteolytic subunit (CLPP)
Mitochondrial complex III
Mitochondrial dysfunction
Mitochondrial protein quality control
Respiratory supercomplexes
UQCRC2 (Core2, Core 2)
Journal
Biochimica et biophysica acta. Molecular basis of disease
ISSN: 1879-260X
Titre abrégé: Biochim Biophys Acta Mol Basis Dis
Pays: Netherlands
ID NLM: 101731730
Informations de publication
Date de publication:
01 08 2021
01 08 2021
Historique:
received:
11
12
2020
revised:
31
03
2021
accepted:
12
04
2021
pubmed:
19
4
2021
medline:
18
11
2021
entrez:
18
4
2021
Statut:
ppublish
Résumé
The mitochondrial respiratory chain (MRC) complex III (CIII) associates with complexes I and IV (CI and CIV) into supercomplexes. We identified a novel homozygous missense mutation (c.665G>C; p.Gly222Ala) in UQCRC2 coding for structural subunit Core 2 in a patient with severe encephalomyopathy. The structural data suggest that the Gly222Ala exchange might result in an altered spatial arrangement in part of the UQCRC2 subunit, which could impact specific protein-protein interactions. Accordingly, we have found decreased levels of CIII and accumulation of CIII-specific subassemblies comprising MT-CYB, UQCRB, UQCRQ, UQCR10 and CYC1 subunits, but devoid of UQCRC1, UQCRC2, and UQCRFS1 in the patient's fibroblasts. The lack of UQCRC1 subunit-containing subassemblies could result from an impaired interaction with mutant UQCRC2
Identifiants
pubmed: 33865955
pii: S0925-4439(21)00080-6
doi: 10.1016/j.bbadis.2021.166147
pii:
doi:
Substances chimiques
Mitochondrial Proteins
0
Electron Transport Complex III
EC 7.1.1.8
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
166147Informations de copyright
Copyright © 2021 Elsevier B.V. All rights reserved.