HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 50, 50316-50321, December 12, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/50/50316    most recent M307763200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhyvoloup, A. Articles by Gout, I. T. Search for Related Content PubMed PubMed Citation Articles by Zhyvoloup, A. Articles by Gout, I. T. Social Bookmarking                      What's this?

Subcellular Localization and Regulation of Coenzyme A Synthase^*

Alexander Zhyvoloup, Ivan Nemazanyy¶, Ganna Panasyuk||**, Taras Valovka, Tim Fenton, Heike Rebholz, Mong-Lien Wang, Richard Foxon, Valeriy Lyzogubov, Vasylij Usenko, Ramziya Kyyamova, Olena Gorbenko, Genadiy Matsuka, Valeriy Filonenko, and Ivan T. Gout¶¶

From the Department of Structure and Function of Nucleic Acid, The Institute of Molecular Biology and Genetics, Kyiv 03143, Ukraine, Ludwig Institute for Cancer Research, London W1W 7BS, United Kingdom, ^||National University "Kyiv-Mohyla Academy," Kyiv 04070, Ukraine, Morphological Laboratory BIONTEC, Dnipropetrovsk 94000, Ukraine, and Department of Biochemistry and Molecular Biology, Royal Free and University College Medical School, London WC1E 6BT, United Kingdom

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.

Received for publication, July 18, 2003 , and in revised form, September 12, 2003.

^* This work was supported in part by grants from the Wellcome Trust, INTAS, the Royal Society and the National Academy of Sciences of Ukraine. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ Supported by a European Association for Cancer Research Travel Fellowship.

^** Supported by a Federation of European Biochemical Societies Summer Fellowship.

^¶¶ To whom reprint requests should be addressed: The Ludwig Institute for Cancer Research, 91 Riding House St., London W1W 7BS, UK. Tel.: 0044-207-8784088; Fax: 0044-207-8784040; E-mail: ivan{at}ludwig.ucl.ac.uk.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S.-J. Reilly, V. Tillander, R. Ofman, S. E.H. Alexson, and M. C. Hunt The Nudix Hydrolase 7 is an Acyl-CoA Diphosphatase Involved in Regulating Peroxisomal Coenzyme A Homeostasis J. Biochem., November 1, 2008; 144(5): 655 - 663. [Abstract] [Full Text] [PDF]

				Y.-M. Zhang, C. O. Rock, and S. Jackowski Biochemical Properties of Human Pantothenate Kinase 2 Isoforms and Mutations Linked to Pantothenate Kinase-associated Neurodegeneration J. Biol. Chem., January 6, 2006; 281(1): 107 - 114. [Abstract] [Full Text] [PDF]