Assembly of The Mitochondrial Complex I Assembly Complex Suggests a Regulatory Role for Deflavination
| العنوان: | Assembly of The Mitochondrial Complex I Assembly Complex Suggests a Regulatory Role for Deflavination |
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| المؤلفون: | Giachin, Gabriele, Jessop, Matthew, Bouverot, Romain, Acajjaoui, Samira, Saïdi, Melissa, Chretien, Anaïs, Bacia‐Verloop, Maria, Signor, Luca, Mas, Philippe J., Favier, Adrien, Borel Meneroud, Eve, Hons, Michael, Hart, Darren J., Kandiah, Eaazhisai, Boeri Erba, Elisabetta, Buisson, Alain, Leonard, Gordon, Gutsche, Irina, Soler‐Lopez, Montserrat |
| المساهمون: | European Synchrotron Radiation Facility (ESRF), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Inserm, U1216, Grenoble, France., Institut National de la Santé et de la Recherche Médicale (INSERM), European Molecular Biology Laboratory [Grenoble] (EMBL), ISBG, ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010), ANR-10-LABX-0049,GRAL,Grenoble Alliance for Integrated Structural Cell Biology(2010), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), European Project: grant number 647784, Thomas, Frank, Infrastructure Française pour la Biologie Structurale Intégrée - - FRISBI2010 - ANR-10-INBS-0005 - INBS - VALID, Grenoble Alliance for Integrated Structural Cell Biology - - GRAL2010 - ANR-10-LABX-0049 - LABX - VALID, CBH-EUR-GS - - CBH-EUR-GS2017 - ANR-17-EURE-0003 - EURE - VALID, European Union’s Horizon 2020 - grant number 647784 - INCOMING |
| المصدر: | Angewandte Chemie International Edition Angewandte Chemie International Edition, Wiley-VCH Verlag, 2020, ⟨10.1002/anie.202011548⟩ Angewandte Chemie International Edition, 2020, ⟨10.1002/anie.202011548⟩ Angewandte Chemie (International Ed. in English) |
| بيانات النشر: | HAL CCSD, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], ACAD9, deflavination, Oxidative Phosphorylation, 03 medical and health sciences, Acyl-CoA Dehydrogenases, mitochondrial complex I assembly complex, Humans, Protein Interaction Domains and Motifs, Cryo-EM, FAD, Research Articles, Adaptor Proteins, Signal Transducing, 030304 developmental biology, 0303 health sciences, Electron Transport Complex I, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Cryoelectron Microscopy, 030302 biochemistry & molecular biology, General Medicine, Recombinant Proteins, Mitochondria, Protein Structure, Tertiary, Flavin-Adenine Dinucleotide, Mitochondrial Pathways, Energy Metabolism, Research Article |
| الوصف: | 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. Fatty acid oxidation (FAO) and oxidative phosphorylation (OXPHOS) are key mitochondrial pathways for cellular energetics. However, the crosstalk between them is unclear. We show that the molecular architecture of the mitochondrial Complex I assembly (MCIA) complex, required for Complex I biogenesis and thereby for activation of OXPHOS, implies an allosteric deflavination mechanism that shuts down FAO. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1433-7851 1521-3773 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::028cea6d5cd7c5b64cac446bae088c69 https://hal.univ-grenoble-alpes.fr/hal-03119718 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....028cea6d5cd7c5b64cac446bae088c69 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14337851 15213773 |
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