PXD044938-2

PXD044938 is an original dataset announced via ProteomeXchange.

Title	Trypanosoma brucei bloodstream form mitochondrion is capable of ATP production by substrate-level phoshorylation
Description	The bloodstream form Trypanosoma brucei maintains its essential mitochondrial membrane potential (ΔΨm) 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 ΔΨm. 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 ΔΨm. In totality, the data establish that the bloodstream form mitochondrion is capable of generating ATP via substrat-level phosphorylation pathways.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:25:45.798.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	F Butter
SpeciesList	scientific name: Trypanosoma brucei; NCBI TaxID: 5691;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-29 11:23:40	ID requested
1	2024-01-26 07:03:36	announced
⏵ 2	2024-10-22 06:25:46	announced	2024-10-22: Updated project metadata.

Taleva G, Husov, á M, Panicucci B, Hierro-Yap C, Pineda E, Biran M, Moos M, Š, imek P, Butter F, Bringaud F, Z, í, kov, á A, Mitochondrion of the Trypanosoma brucei long slender bloodstream form is capable of ATP production by substrate-level phosphorylation. PLoS Pathog, 19(10):e1011699(2023) [pubmed]

10.1371/journal.ppat.1011699;

submitter keyword: LC-MS/MS

Falk Butter
contact affiliation	Institute of Molecular Biology (IMB)
contact email	f.butter@imb.de
lab head
F Butter
contact affiliation	Quantitative Proteomics Institute of Molecular Biology (IMB)
contact email	f.butter@imb-mainz.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/01/PXD044938

PRIDE project URI

• PRIDE
  1. PXD044938
     1. Label: PRIDE project
     2. Name: Trypanosoma brucei bloodstream form mitochondrion is capable of ATP production by substrate-level phoshorylation