Mitochondrion of the Trypanosoma brucei long slender bloodstream form is capable of ATP production by substrate-level phosphorylation
| dc.rights.license | open | en_US |
| hal.structure.identifier | University of South Bohemia | |
| dc.contributor.author | TALEVA, Gergana | |
| hal.structure.identifier | University of South Bohemia | |
| dc.contributor.author | HUSOVÁ, Michaela | |
| hal.structure.identifier | University of South Bohemia | |
| dc.contributor.author | PANICUCCI, Brian | |
| hal.structure.identifier | University of South Bohemia | |
| dc.contributor.author | HIERRO-YAP, Carolina | |
| hal.structure.identifier | Microbiologie Fondamentale et Pathogénicité [MFP] | |
| dc.contributor.author | PINEDA, Eric | |
| hal.structure.identifier | University of South Bohemia | |
| dc.contributor.author | MOOS, Martin | |
| hal.structure.identifier | University of South Bohemia | |
| dc.contributor.author | ŠIMEK, Petr | |
| hal.structure.identifier | Friedrich-Loeffler-Institute, German National Reference Centre for Human and Animal Brucellosis, Jena, Germany | |
| dc.contributor.author | BUTTER, Falk | |
| hal.structure.identifier | Microbiologie Fondamentale et Pathogénicité [MFP] | |
| dc.contributor.author | BRINGAUD, Frédéric | |
| hal.structure.identifier | University of South Bohemia | |
| dc.contributor.author | ZÍKOVÁ, Alena | |
| dc.date.accessioned | 2023-11-16T12:53:30Z | |
| dc.date.available | 2023-11-16T12:53:30Z | |
| dc.date.issued | 2023-10-11 | |
| dc.identifier.issn | 1553-7366 | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/184816 | |
| dc.description.abstractEn | The long slender bloodstream form Trypanosoma brucei maintains its essential mitochondrial membrane potential (ΔΨm) through the proton-pumping activity of the F o F 1-ATP synthase operating in the reverse mode. The ATP that drives this hydrolytic reaction has long been thought to be generated by glycolysis and imported from the cytosol via an ATP/ADP carrier (AAC). Indeed, we demonstrate that AAC is the only carrier that can import ATP into the mitochondrial matrix to power the hydrolytic activity of the F o F 1-ATP synthase. However, contrary to expectations, the deletion of AAC has no effect on parasite growth, virulence or levels of ΔΨ m. This suggests that ATP is produced by substrate-level phosphorylation pathways in the mitochondrion. Therefore, we knocked out the succinyl-CoA synthetase (SCS) gene, a key mitochondrial enzyme that produces ATP through substrate-level phosphorylation in this parasite. Its absence resulted in changes to the metabolic landscape of the parasite, lowered virulence, and reduced mitochondrial ATP content. Strikingly, these SCS mutant parasites become more dependent on AAC as demonstrated by a 25-fold increase in their sensitivity to the AAC inhibitor, carboxyatractyloside. Since the parasites were able to adapt to the loss of SCS in culture, we also analyzed the more immediate phenotypes that manifest when SCS expression is rapidly suppressed by RNAi. Importantly, when performed under nutrient-limited conditions mimicking various host environments, SCS depletion strongly affected parasite growth and levels of ΔΨ m. In totality, the data establish that the bloodstream form mitochondrion is capable of generating ATP via substrate-level phosphorylation pathways. | |
| dc.language.iso | EN | en_US |
| dc.title.en | Mitochondrion of the Trypanosoma brucei long slender bloodstream form is capable of ATP production by substrate-level phosphorylation | |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1371/journal.ppat.1011699 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio] | en_US |
| bordeaux.journal | PLoS Pathogens | en_US |
| bordeaux.page | e1011699 | en_US |
| bordeaux.volume | 19 | en_US |
| bordeaux.hal.laboratories | Centre de Résonance Magnétique des Systèmes Biologiques (CRMSB) - UMR 5536 | en_US |
| bordeaux.issue | 10 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.institution | CNRS | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| bordeaux.import.source | hal | |
| hal.identifier | hal-04242342 | |
| hal.version | 1 | |
| hal.popular | non | en_US |
| hal.audience | Internationale | en_US |
| hal.export | false | |
| workflow.import.source | hal | |
| 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=PLoS%20Pathogens&rft.date=2023-10-11&rft.volume=19&rft.issue=10&rft.spage=e1011699&rft.epage=e1011699&rft.eissn=1553-7366&rft.issn=1553-7366&rft.au=TALEVA,%20Gergana&HUSOV%C3%81,%20Michaela&PANICUCCI,%20Brian&HIERRO-YAP,%20Carolina&PINEDA,%20Eric&rft.genre=article |
