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

J. Biol. Chem., Vol. 280, Issue 37, 32434-32441, September 16, 2005

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 280/37/32434    most recent M503152200v1 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 Mizuarai, S. Articles by Kotani, H. Search for Related Content PubMed PubMed Citation Articles by Mizuarai, S. Articles by Kotani, H. Social Bookmarking                      What's this?

Identification of Dicarboxylate Carrier Slc25a10 as Malate Transporter in de Novo Fatty Acid Synthesis^*

From the Tsukuba Research Institute, Banyu Pharmaceutical Co. Ltd., Okubo 3, Tsukuba, Ibaraki 300-2611, Japan

Mitochondrial solute carrier family 25 member 10 (Slc25a10) transports dicarboxylates such as malate or succinate across the mitochondrial inner membrane. Although fatty acid synthesis in adipose tissue or the liver is initiated by citrate transport in exchange for malate across the mitochondrial membrane, the transporter responsible for supplying malate during citrate transport has not been identified. In the present study, we clarified the role of Slc25a10 in supplying malate for citrate transport and examined the effect of Slc25a10 suppression on the lipogenic pathway and lipid accumulation. We have reported an Slc25a10 increase in white adipose tissue in obese mouse models and a decrease in a fasted mouse model using expression profiles. Next, we examined the effect of Slc25a10 suppression by small interfering RNA on citrate transport in the lipogenic cell lines HepG2 and 3T3-L1. We observed that inhibition of malate transport by Slc25a10 suppression significantly reduced the citrate transport from the mitochondria to the cytosol. We also found that suppression of Slc25a10 down-regulated the lipogenic pathway, indicated by decreases in ACC1 expression and malonyl-CoA level. Furthermore, suppression of Slc25a10 decreased triglyceride lipid accumulation in adipose-differentiated 3T3-L1 cells. These results suggested that Slc25a10 plays an important role in supplying malate for citrate transport required for fatty acid synthesis and indicated that inhibition of Slc25a10 might effectively reduce lipid accumulation in adipose tissues.

Received for publication, March 22, 2005 , and in revised form, June 23, 2005.

^* 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.

The on-line version of this article (available at http://www.jbc.org) contains a supplemental table and a supplemental figure.

¹ To whom correspondence should be addressed. Tel.: 81-29-877-2202; Fax: 81-29-877-2027; E-mail: hidehito_kotani{at}merck.com.

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

This article has been cited by other articles:

				C. A. Piantadosi and H. B. Suliman Transcriptional Regulation of SDHa Flavoprotein by Nuclear Respiratory Factor-1 Prevents Pseudo-hypoxia in Aerobic Cardiac Cells J. Biol. Chem., April 18, 2008; 283(16): 10967 - 10977. [Abstract] [Full Text] [PDF]

				C. Guay, S. R. M. Madiraju, A. Aumais, E. Joly, and M. Prentki A Role for ATP-Citrate Lyase, Malic Enzyme, and Pyruvate/Citrate Cycling in Glucose-induced Insulin Secretion J. Biol. Chem., December 7, 2007; 282(49): 35657 - 35665. [Abstract] [Full Text] [PDF]

				Z. Ma, N. Portwood, D. Brodin, V. Grill, and A. Bjorklund Effects of Diazoxide on Gene Expression in Rat Pancreatic Islets Are Largely Linked to Elevated Glucose and Potentially Serve to Enhance {beta}-Cell Sensitivity Diabetes, April 1, 2007; 56(4): 1095 - 1106. [Abstract] [Full Text] [PDF]