Biochemical consequences of two clinically relevant ND-gene mutations in Escherichia coli respiratory complex I
| dc.rights.license | open | en_US |
| dc.contributor.author | NUBER, Franziska | |
| dc.contributor.author | SCHIMPF, Johannes | |
| hal.structure.identifier | Institut de biochimie et génétique cellulaires [IBGC] | |
| dc.contributor.author | DI RAGO, Jean-Paul | |
| hal.structure.identifier | Institut de biochimie et génétique cellulaires [IBGC] | |
| dc.contributor.author | TRIBOUILLARD TANVIER, Deborah | |
| dc.contributor.author | PROCACCIO, Vincent | |
| hal.structure.identifier | Institut des Maladies Neurodégénératives [Bordeaux] [IMN] | |
| dc.contributor.author | MARTIN-NEGRIER, Marie-Laure | |
| hal.structure.identifier | Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM] | |
| dc.contributor.author | TRIMOUILLE, Aurelien | |
| dc.contributor.author | BINER, Olivier | |
| dc.contributor.author | VON BALLMOOS, Christophe | |
| dc.contributor.author | FRIEDRICH, Thorsten | |
| dc.date.accessioned | 2021-10-26T08:47:10Z | |
| dc.date.available | 2021-10-26T08:47:10Z | |
| dc.date.issued | 2021-06-16 | |
| dc.identifier.issn | 2045-2322 | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/112871 | |
| dc.description.abstractEn | NADH:ubiquinone oxidoreductase (respiratory complex I) plays a major role in energy metabolism by coupling electron transfer from NADH to quinone with proton translocation across the membrane. Complex I deficiencies were found to be the most common source of human mitochondrial dysfunction that manifest in a wide variety of neurodegenerative diseases. Seven subunits of human complex I are encoded by mitochondrial DNA (mtDNA) that carry an unexpectedly large number of mutations discovered in mitochondria from patients’ tissues. However, whether or how these genetic aberrations affect complex I at a molecular level is unknown. Here, we used Escherichia coli as a model system to biochemically characterize two mutations that were found in mtDNA of patients. The V253AMT-ND5 mutation completely disturbed the assembly of complex I, while the mutation D199GMT-ND1 led to the assembly of a stable complex capable to catalyze redox-driven proton translocation. However, the latter mutation perturbs quinone reduction leading to a diminished activity. D199MT-ND1 is part of a cluster of charged amino acid residues that are suggested to be important for efficient coupling of quinone reduction and proton translocation. A mechanism considering the role of D199MT-ND1 for energy conservation in complex I is discussed. | |
| dc.language.iso | EN | en_US |
| dc.rights | Attribution 3.0 United States | * |
| dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | * |
| dc.title.en | Biochemical consequences of two clinically relevant ND-gene mutations in Escherichia coli respiratory complex I | |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1038/s41598-021-91631-3 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Médecine humaine et pathologie | en_US |
| dc.identifier.pubmed | 34135385 | en_US |
| bordeaux.journal | Scientific Reports | en_US |
| bordeaux.volume | 11 | en_US |
| bordeaux.hal.laboratories | Maladies Rares : Génétique et Métabolisme (MRGM) - UMR 1211 | en_US |
| bordeaux.issue | 1 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.institution | INSERM | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| bordeaux.identifier.funderID | Deutsche Forschungsgemeinschaft | en_US |
| hal.identifier | hal-03403436 | |
| hal.version | 1 | |
| hal.date.transferred | 2021-10-26T08:47:15Z | |
| hal.export | true | |
| dc.rights.cc | Pas de Licence CC | en_US |
| bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Scientific%20Reports&rft.date=2021-06-16&rft.volume=11&rft.issue=1&rft.eissn=2045-2322&rft.issn=2045-2322&rft.au=NUBER,%20Franziska&SCHIMPF,%20Johannes&DI%20RAGO,%20Jean-Paul&TRIBOUILLARD%20TANVIER,%20Deborah&PROCACCIO,%20Vincent&rft.genre=article |
