1. Assembly of The Mitochondrial Complex I Assembly Complex Suggests a Regulatory Role for Deflavination.
- Author
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Giachin G, Jessop M, Bouverot R, Acajjaoui S, Saïdi M, Chretien A, Bacia-Verloop M, Signor L, Mas PJ, Favier A, Borel Meneroud E, Hons M, Hart DJ, Kandiah E, Boeri Erba E, Buisson A, Leonard G, Gutsche I, and Soler-Lopez M
- Subjects
- Acyl-CoA Dehydrogenases genetics, Acyl-CoA Dehydrogenases metabolism, Adaptor Proteins, Signal Transducing chemistry, Adaptor Proteins, Signal Transducing metabolism, Cryoelectron Microscopy, Electron Transport Complex I metabolism, Energy Metabolism, Flavin-Adenine Dinucleotide chemistry, Humans, Oxidative Phosphorylation, Protein Interaction Domains and Motifs, Protein Structure, Tertiary, Recombinant Proteins biosynthesis, Recombinant Proteins chemistry, Recombinant Proteins isolation & purification, Electron Transport Complex I chemistry, Flavin-Adenine Dinucleotide metabolism, Mitochondria metabolism
- Abstract
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., (© 2020 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
- Published
- 2021
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