ArticleBiochimica et biophysica acta. Bioenergetics2020
The ASCT/SCS cycle fuels mitochondrial ATP and acetate production in Trypanosoma brucei.
Article in Biochimica et biophysica acta. Bioenergetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 25 citations in OpenAlex.
- Succinate and lactate produced as conserved biomarkers through chronic and transient substrate-level phosphorylation: from microorganisms to cancer.Journal of bioenergetics and biomembranes · 2026Review
- Modulation of succinyl-CoA:3-ketoacid CoA transferase activity by a single amino acid residue in acetate:succinate CoA transferase from Trypanosoma brucei, the causative agent of African sleeping sickness.Protein science : a publication of the Protein Society · 2026Article
- Mycorrhizal colonization of dryland tree establishment depends on soil microbial cooperation.Nature communications · 2025Article
- Energy metabolism inmBio · 2025Review
- Development of tolerance to bedaquiline by overexpression of trypanosomal acetate: succinate CoA transferase in Mycobacterium smegmatis.Communications biology · 2025Article
- Bacterial acetate metabolism and its influence on human epithelia.Emerging topics in life sciences · 2024Review
- Gene Expression of Ethanol and Acetate Metabolic Pathways in theMicroorganisms · 2024Article
- Mitochondrion of the Trypanosoma brucei long slender bloodstream form is capable of ATP production by substrate-level phosphorylation.PLoS pathogens · 2023Article
- How much (ATP) does it cost to build a trypanosome? A theoretical study on the quantity of ATP needed to maintain and duplicate a bloodstream-form Trypanosoma brucei cell.PLoS pathogens · 2023Article
- Metabolic insights into phosphofructokinase inhibition in bloodstream-form trypanosomes.Frontiers in cellular and infection microbiology · 2023Article
- Redefining the coenzyme A transferase superfamily with a large set of manually annotated proteins.Protein science : a publication of the Protein Society · 2022Article
- Trypanosoma brucei: Metabolomics for analysis of cellular metabolism and drug discovery.Metabolomics : Official journal of the Metabolomic Society · 2022Review
- Succinyl-CoA:acetate CoA-transferase functioning in the oxidative tricarboxylic acid cycle inFrontiers in microbiology · 2022Article
- Divergent metabolism between Trypanosoma congolense and Trypanosoma brucei results in differential sensitivity to metabolic inhibition.PLoS pathogens · 2021Article
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13 authors at 5 institutions in 4 countries.
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No grant is acknowledged in the PubMed record.
Abstract
Acetate:succinate CoA transferase (ASCT) is a mitochondrial enzyme that catalyzes the production of acetate and succinyl-CoA, which is coupled to ATP production with succinyl-CoA synthetase (SCS) in a process called the ASCT/SCS cycle. This cycle has been studied in Trypanosoma brucei (T. brucei), a pathogen of African sleeping sickness, and is involved in (i) ATP and (ii) acetate production and proceeds independent of oxygen and an electrochemical gradient. Interestingly, knockout of ASCT in procyclic form (PCF) of T. brucei cause oligomycin A-hypersensitivity phenotype indicating that ASCT/SCS cycle complements the deficiency of ATP synthase activity. In bloodstream form (BSF) of T. brucei, ATP synthase works in reverse to maintain the electrochemical gradient by hydrolyzing ATP. However, no information has been available on the source of ATP, although ASCT/SCS cycle could be a potential candidate. Regarding mitochondrial acetate production, which is essential for fatty acid biosynthesis and growth of T. brucei, ASCT or acetyl-CoA hydrolase (ACH) are known to be its source. Despite the importance of this cycle, direct evidence of its function is lacking, and there are no comprehensive biochemical or structural biology studies reported so far. Here, we show that in vitro-reconstituted ASCT/SCS cycle is highly specific towards acetyl-CoA and has a higher k
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