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Subcellular localization and regulation of coenzyme a synthase

Zhyvoloup, A, Nemazanyy, I, Panasyuk, G, Valovka, T, Fenton, TR, Rebholz, H, Wang, ML, Foxon, R, Lyzogubov, V, Usenko, V, and others. (2003) Subcellular localization and regulation of coenzyme a synthase. Journal of Biological Chemistry, 278 (50). 50316 - 50321. ISSN 0021-9258. (doi:10.1074/jbc.M307763200) (KAR id:61527)

Abstract

CoA synthase mediates the last two steps in the sequence of enzymatic reactions, leading to CoA biosynthesis. We have recently identified cDNA for CoA synthase and demonstrated that it encodes a bifunctional enzyme possessing 4'-phosphopantetheine adenylyltransferase and dephospho-CoA kinase activities. Molecular cloning of CoA synthase provided us with necessary tools to study subcellular localization and the regulation of this bifunctional enzyme. Transient expression studies and confocal microscopy allowed us to demonstrate that full-length CoA synthase is associated with the mitochondria, whereas the removal of the N-terminal region relocates the enzyme to the cytosol. In addition, we showed that the N-terminal sequence of CoA synthase ( amino acids 1 - 29) exhibits a hydrophobic profile and targets green fluorescent protein exclusively to mitochondria. Further analysis, involving subcellular fractionation and limited proteolysis, indicated that CoA synthase is localized on the mitochondrial outer membrane. Moreover, we demonstrate for the first time that phosphatidylcholine and phosphatidylethanolamine, which are the main components of the mitochondrial outer membrane, are potent activators of both enzymatic activities of CoA synthase in vitro. Taken together, these data provide the evidence that the final stages of CoA biosynthesis take place on mitochondria and the activity of CoA synthase is regulated by phospholipids.

Item Type: Article
DOI/Identification number: 10.1074/jbc.M307763200
Uncontrolled keywords: SYNTHESIZING PROTEIN COMPLEX, MITOCHONDRIAL CONTACT SITES, PANTOTHENATE KINASE, RAT-LIVER, COA BIOSYNTHESIS, ACETYL-COA, HEART, MEMBRANE, METABOLISM, CARNITINE
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Tim Fenton
Date Deposited: 19 Dec 2018 06:27 UTC
Last Modified: 16 Nov 2021 10:24 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/61527 (The current URI for this page, for reference purposes)

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