Mitochondrion of the Trypanosoma brucei long slender bloodstream form is capable of ATP production by substrate-level phosphorylation

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F23%3A00580603" target="_blank" >RIV/60077344:_____/23:00580603 - isvavai.cz</a>

Alternative codes found

RIV/60076658:12310/23:43907131

Result on the web

<a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1011699" target="_blank" >https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1011699</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1371/journal.ppat.1011699" target="_blank" >10.1371/journal.ppat.1011699</a>

Result language

angličtina

Original language name

Mitochondrion of the Trypanosoma brucei long slender bloodstream form is capable of ATP production by substrate-level phosphorylation

Original language description

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.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10601 - Cell biology

Project

<a href="/en/project/GA20-14409S" target="_blank" >GA20-14409S: A paradigm shift for Trypanosoma brucei ATP production: rewiring of mitochondrial metabolism allows for the infection of various host environments</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

PLoS Pathogens

ISSN

1553-7366

e-ISSN

1553-7374

Volume of the periodical

19

Issue of the periodical within the volume

10

Country of publishing house

US - UNITED STATES

Number of pages

31

Pages from-to

e1011699

UT code for WoS article

001087349200002

EID of the result in the Scopus database

2-s2.0-85173682907