A membrane arm of mitochondrial complex I sufficient to promote respirasome formation.
Cell Rep
; 35(2): 108963, 2021 04 13.
Article
em En
| MEDLINE
| ID: mdl-33852835
ABSTRACT
The assembly pathways of mitochondrial respirasome (supercomplex I+III2+IV) are not fully understood. Here, we show that an early sub-complex I assembly, rather than holo-complex I, is sufficient to initiate mitochondrial respirasome assembly. We find that a distal part of the membrane arm of complex I (PD-a module) is a scaffold for the incorporation of complexes III and IV to form a respirasome subcomplex. Depletion of PD-a, rather than other complex I modules, decreases the steady-state levels of complexes III and IV. Both HEK293T cells lacking TIMMDC1 and patient-derived cells with disease-causing mutations in TIMMDC1 showed accumulation of this respirasome subcomplex. This suggests that TIMMDC1, previously known as a complex-I assembly factor, may function as a respirasome assembly factor. Collectively, we provide a detailed, cooperative assembly model in which most complex-I subunits are added to the respirasome subcomplex in the lateral stages of respirasome assembly.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Complexo IV da Cadeia de Transporte de Elétrons
/
Complexo III da Cadeia de Transporte de Elétrons
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Complexo I de Transporte de Elétrons
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Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial
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Mitocôndrias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article