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

This Article Full Text Full Text (PDF) All Versions of this Article: 296/4/E647    most recent 90761.2008v1 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 Cao, J. Articles by Shi, Y. Search for Related Content PubMed PubMed Citation Articles by Cao, J. Articles by Shi, Y.

ALCAT1 is a polyglycerophospholipid acyltransferase potently regulated by adenine nucleotide and thyroid status

¹Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; ²Institute of Molecular and Experimental Therapeutics, East China Normal University, Shanghai; and ³Department of Biological Sciences and Biotechnology, School of Medicine, Tsinghua University, Beijing, China

Submitted 29 September 2008 ; accepted in final form 20 December 2008

Acyl-CoA:lysocardiolipin acyltransferase-1 (ALCAT1) catalyzes acylation of lysocardiolipin back to cardiolipin, an important step in cardiolipin remodeling. The present study reports the catalytic properties of ALCAT1 in vitro and its regulation by thyroid hormone status in mouse liver and heart. Recombinant ALCAT1 expressed in Sf9 cells preferred basic pH conditions and did not require divalent cations or integrity of the subcellular membrane for its enzymatic activity. Recombinant ALCAT1 was potently inhibited by ADP and ATP, but not by adenosine nucleotide analogs or other nucleotides, such as UTP and GTP, suggesting that ALCAT1 does not require ATP hydrolysis for its enzyme activity. In addition to cardiolipin, ALCAT1 also catalyzed acylation of other members of the polyglycerophospholipid family, including phosphatidylglycerol, a precursor for cardiolipin synthesis, and bis(monoacylglycero)phosphate, a structural isomer of lysophosphatidylglycerol and a metabolic intermediate of cardiolipin. These findings suggest that ALCAT1 plays a role in the remodeling of other polyglycerophospholipids. In support of a regulatory role of ALCAT1 in cardiolipin remodeling in response to oxidative stress, ALCAT1 expression in liver and heart was significantly downregulated in mice with hypothyroidism and upregulated in mice treated with thyroid hormone, which is known to stimulate mitochondrial activity, oxidative stress, and cardiolipin remodeling.

cardiolipin remodeling; oxidative stress; reactive oxygen species; hyperthyroidism; monolysocardiolipin acyltransferase

This article has been cited by other articles:

				W. A. Taylor and G. M. Hatch Identification of the Human Mitochondrial Linoleoyl-coenzyme A Monolysocardiolipin Acyltransferase (MLCL AT-1) J. Biol. Chem., October 30, 2009; 284(44): 30360 - 30371. [Abstract] [Full Text] [PDF]