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Mitochondrion of the Trypanosoma brucei long slender bloodstream form is capable of ATP production by substrate-level phosphorylation
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SYSNO ASEP 0580603 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Mitochondrion of the Trypanosoma brucei long slender bloodstream form is capable of ATP production by substrate-level phosphorylation Tvůrce(i) Taleva, Gergana (BC-A) SAI
Husová, Michaela (BC-A) ORCID
Panicucci, Brian (BC-A)
Hierro-Yap, Carolina (BC-A) ORCID
Pineda, E. (FR)
Biran, M. (FR)
Moos, Martin (BC-A) RID, ORCID
Šimek, Petr (BC-A) RID, ORCID
Butter, F. (DE)
Bringaud, F. (FR)
Zíková, Alena (BC-A) RID, ORCIDCelkový počet autorů 11 Číslo článku e1011699 Zdroj.dok. PLoS Pathogens. - : Public Library of Science - ISSN 1553-7366
Roč. 19, č. 10 (2023)Poč.str. 31 s. Forma vydání Online - E Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova inducible expression system ; succinate coa-transferase ; trypanocidal action ; lipid biosynthesis ; acetate ; fractionation ; complex Vědní obor RIV EA - Morfologické obory a cytologie Obor OECD Cell biology CEP GA20-14409S GA ČR - Grantová agentura ČR Způsob publikování Open access Institucionální podpora BC-A - RVO:60077344 UT WOS 001087349200002 EID SCOPUS 85173682907 DOI 10.1371/journal.ppat.1011699 Anotace The long slender bloodstream form Trypanosoma brucei maintains its essential mitochondrial membrane potential (Delta psi m) through the proton-pumping activity of the FoF1-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 FoF1-ATP synthase. However, contrary to expectations, the deletion of AAC has no effect on parasite growth, virulence or levels of Delta psi 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 Delta psi m. In totality, the data establish that the long slender bloodstream form mitochondrion is capable of generating ATP via substrate-level phosphorylation pathways. Pracoviště Biologické centrum (od r. 2006) Kontakt Dana Hypšová, eje@eje.cz, Tel.: 387 775 214 Rok sběru 2024 Elektronická adresa https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1011699
Počet záznamů: 1