Assembly of The Mitochondrial Complex I Assembly Complex Suggests a Regulatory Role for Deflavination.
Acyl-CoA Dehydrogenases
/ genetics
Adaptor Proteins, Signal Transducing
/ chemistry
Cryoelectron Microscopy
Electron Transport Complex I
/ chemistry
Energy Metabolism
Flavin-Adenine Dinucleotide
/ chemistry
Humans
Mitochondria
/ metabolism
Oxidative Phosphorylation
Protein Interaction Domains and Motifs
Protein Structure, Tertiary
Recombinant Proteins
/ biosynthesis
ACAD9
Cryo-EM
FAD
deflavination
mitochondrial complex I assembly complex
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
23 02 2021
23 02 2021
Historique:
received:
23
08
2020
pubmed:
16
12
2020
medline:
26
3
2021
entrez:
15
12
2020
Statut:
ppublish
Résumé
Fatty acid β-oxidation (FAO) and oxidative phosphorylation (OXPHOS) are mitochondrial redox processes that generate ATP. The biogenesis of the respiratory Complex I, a 1 MDa multiprotein complex that is responsible for initiating OXPHOS, is mediated by assembly factors including the mitochondrial complex I assembly (MCIA) complex. However, the organisation and the role of the MCIA complex are still unclear. Here we show that ECSIT functions as the bridging node of the MCIA core complex. Furthermore, cryo-electron microscopy together with biochemical and biophysical experiments reveal that the C-terminal domain of ECSIT directly binds to the vestigial dehydrogenase domain of the FAO enzyme ACAD9 and induces its deflavination, switching ACAD9 from its role in FAO to an MCIA factor. These findings provide the structural basis for the MCIA complex architecture and suggest a unique molecular mechanism for coordinating the regulation of the FAO and OXPHOS pathways to ensure an efficient energy production.
Identifiants
pubmed: 33320993
doi: 10.1002/anie.202011548
pmc: PMC7986633
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Ecsit protein, human
0
Recombinant Proteins
0
Flavin-Adenine Dinucleotide
146-14-5
Acyl-CoA Dehydrogenases
EC 1.3.-
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
4689-4697Informations de copyright
© 2020 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.
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