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J. Biol. Chem., Vol. 280, Issue 23, 22036-22043, June 10, 2005

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A New Renal Mitochondrial Carrier, KMCP1, Is Up-regulated during Tubular Cell Regeneration and Induction of Antioxidant Enzymes^*

Anne Haguenauer, Serge Raimbault, Sandrine Masscheleyn, Maria del Mar Gonzalez-Barroso, Francois Criscuolo, Julie Plamondon, Bruno Miroux, Daniel Ricquier, Denis Richard, Frederic Bouillaud, and Claire Pecqueur¶

From the CNRS UPR9078, Faculté Necker-Enfants Malades, 156 Rue de Vaugirard, 75730 Paris Cedex 15, France and the Département d'Anatomie et de Physiologie, Faculté de Médecine, Université Laval, Quebec G1K 7P4, Canada

The mitochondrial carrier family transports a variety of metabolites across the inner mitochondrial membrane. We identified and cloned a new member of this family, KMCP1 (kidney mitochondrial carrier protein-1), that is highly homologous to the previously identified protein BMCP1 (brain mitochondrial carrier protein-1). Western blotting and in situ experiments showed that this carrier is expressed predominantly within the kidney cortex in the proximal and distal tubules. KMCP1 was increased during fasting and during the regenerative phase of glycerol-induced renal failure. We show that both situations are associated with transiently increased expression of superoxide-generating enzymes, followed by increased mitochondrial metabolism and antioxidant defenses. Given that KMCP1 expression occurs simultaneously with these latter events, we propose that KMCP1 is involved in situations in which mitochondrial metabolism is increased, in particular when the cellular redox balance tends toward a pro-oxidant status.

Received for publication, October 26, 2004 , and in revised form, March 29, 2005.

^* This work was supported by CNRS and by European Community Sixth Framework Program Contract LSHM-CT-2003-503041. 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.

This paper is dedicated to the memory of Serge Raimbault.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) NM_026232 and NM_001010875.

Deceased.

^¶ To whom correspondence should be addressed. Tel.: 33-1-4061-5697; Fax: 33-1-4061-5673; E-mail: pecqueuc{at}necker.fr.

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