About: The ASCT/SCS cycle fuels mitochondrial ATP and acetate production in Trypanosoma brucei

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About: The ASCT/SCS cycle fuels mitochondrial ATP and acetate production in Trypanosoma brucei Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	The ASCT/SCS cycle fuels mitochondrial ATP and acetate production in Trypanosoma brucei
Creator	Boshart, Michael Hirayama, Kenji Balogun, Emmanuel Kita, Kiyoshi Bringaud, Frédéric Fukuda, Keisuke Harada, Shigeharu Inaoka, Daniel Kurasawa, Hana Mazet, Muriel Millerioux, Yoann Mochizuki, Kota Shiba, Tomoo
Source	Elsevier; Medline; PMC
abstract	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 cat than that of yeast and bacterial ATP synthases. Our results provide the first biochemical basis for (i) rescue of ATP synthase-deficient phenotype by ASCT/SCS cycle in PCF and (ii) a potential source of ATP for the reverse reaction of ATP synthase in BSF.
has issue date	2020-08-04(xsd:dateTime)
bibo:doi	10.1016/j.bbabio.2020.148283
bibo:pmid	32763239
has license	els-covid
sha1sum (hex)	c82c6bf55ba7bbc29c79d6f2231ee54cbf6c97dc
schema:url	https://doi.org/10.1016/j.bbabio.2020.148283
resource representing a document's title	The ASCT/SCS cycle fuels mitochondrial ATP and acetate production in Trypanosoma brucei
has PubMed Central identifier	PMC7402102
has PubMed identifier	32763239
schema:publication	Biochim Biophys Acta Bioenerg
resource representing a document's body	covid:c82c6bf55ba7bbc29c79d6f2231ee54cbf6c97dc#body_text
is schema:about of	named entity 'production' named entity 'ASCT' named entity 'Trypanosoma' named entity 'ATP' named entity 'mitochondrial' named entity 'fuels' named entity 'COA TRANSFERASE' named entity 'knockout' named entity 'independent' named entity 'enzyme' named entity 'production' named entity 'acetate' named entity 'succinate' named entity 'Trypanosoma brucei' named entity 'ATP' named entity 'Trypanosoma brucei' named entity 'mitochondrial' named entity 'ATP' named entity 'acetoacetate' named entity 'amino acid metabolism' named entity 'ATP' named entity 'expression vector' named entity 'succinate' named entity 'gene' named entity 'T. brucei' named entity 'salivary glands' named entity 'succinyl-CoA' named entity 'biochemical' named entity 'thiol group' named entity 'pyruvate' named entity 'Tet repressor' named entity 'HCl' named entity 'blood meals' named entity 'electrochemical gradient' named entity 'livestock' named entity 'glycerol' named entity 'Protein' named entity 'Protein' named entity 'genome' named entity 'succinyl-CoA' named entity 'ATP' named entity 'enzyme' named entity 'CoA' named entity 'mitochondrial' named entity 'CoA-transferase' named entity 'CoA' named entity '16.6' named entity 'thiobenzoic acid' named entity 'crystal structure' named entity 'excreted' named entity 'CoA' named entity 'RNAi knockdown' named entity 'enzyme' named entity 'mitochondrial' named entity 'acetate' named entity 'structural biology' named entity 'succinate' named entity 'mitochondrial' named entity 'puromycin' named entity 'life cycle' named entity 'parasite' named entity 'Escherichia coli' named entity 'monomers' named entity 'trypanosomatid' named entity 'acetate' named entity 'acetoacetyl-CoA' named entity 'succinate' named entity 'catalytic mechanism' named entity 'acetyl-CoA'

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