PUBLICATION
A membrane arm of mitochondrial complex I sufficient to promote respirasome formation
- Authors
- Fang, H., Ye, X., Xie, J., Li, Y., Li, H., Bao, X., Yang, Y., Lin, Z., Jia, M., Han, Q., Zhu, J., Li, X., Zhao, Q., Yang, Y., Lyu, J.
- ID
- ZDB-PUB-220215-18
- Date
- 2021
- Source
- Cell Reports 35: 108963 (Journal)
- Registered Authors
- Keywords
- Leigh syndrome, TIMMDC1, cooperative assembly, mitochondrial respirasome, oxidative phosphorylation
- MeSH Terms
-
- Animals
- B-Lymphocytes
- Cell Line, Transformed
- Developmental Disabilities/genetics
- Developmental Disabilities/metabolism
- Developmental Disabilities/pathology
- Electron Transport Complex I/antagonists & inhibitors
- Electron Transport Complex I/genetics*
- Electron Transport Complex I/metabolism
- Electron Transport Complex III/antagonists & inhibitors
- Electron Transport Complex III/genetics*
- Electron Transport Complex III/metabolism
- Electron Transport Complex IV/antagonists & inhibitors
- Electron Transport Complex IV/genetics*
- Electron Transport Complex IV/metabolism
- Embryo, Nonmammalian
- Gene Expression Regulation, Developmental
- HEK293 Cells
- Humans
- Mitochondria/genetics*
- Mitochondria/metabolism
- Mitochondrial Membranes/metabolism
- Mitochondrial Precursor Protein Import Complex Proteins/deficiency
- Mitochondrial Precursor Protein Import Complex Proteins/genetics*
- Morpholinos/genetics
- Morpholinos/metabolism
- Muscle Hypotonia/genetics
- Muscle Hypotonia/metabolism
- Muscle Hypotonia/pathology
- Oxidative Phosphorylation
- Zebrafish
- PubMed
- 33852835 Full text @ Cell Rep.
Citation
Fang, H., Ye, X., Xie, J., Li, Y., Li, H., Bao, X., Yang, Y., Lin, Z., Jia, M., Han, Q., Zhu, J., Li, X., Zhao, Q., Yang, Y., Lyu, J. (2021) A membrane arm of mitochondrial complex I sufficient to promote respirasome formation. Cell Reports. 35:108963.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping