BMCP1, a Novel Mitochondrial Carrier with High Expression in the Central Nervous System of Humans and Rodents, and Respiration Uncoupling Activity in Recombinant Yeast

Daniel Sanchis,Christophe Fleury,Nathalie Chomiki,Marc Goubern,Quinling Huang,Maria Neverova,Francine Grégoire,Juliet Easlick,Serge Raimbault,Corinne Lévi-Meyrueis,Bruno Miroux,Sheila Collins,Michael Seldin,Denis Richard,Craig Warden,Frédéric Bouillaud,Daniel Ricquier

doi:10.1074/jbc.273.51.34611

Abstract

We report here the cloning and functional analysis of a novel homologue of the mitochondrial carriers predominantly expressed in the central nervous system and referred to as BMCP1 (brain mitochondrial carrier protein-1). The predicted amino acid sequence of this novel mitochondrial carrier indicates a level of identity of 39, 31, or 30%, toward the mitochondrial oxoglutarate carrier, phosphate carrier, or adenine nucleotide translocator, respectively, and a level of identity of 34, 38, or 39% with the mitochondrial uncoupling proteins UCP1, UCP2, or UCP3, respectively. Northern analysis of mouse, rat, or human tissues demonstrated that mRNA of this novel gene is mainly expressed in brain, although it is 10-30-fold less expressed in other tissues. In situ hybridization analysis of brain showed it is particularly abundant in cortex, hippocampus, thalamus, amygdala, and hypothalamus. Chromosomal mapping indicates that BMCP1 is located on chromosome X of mice and at Xq24 in man. Expression of the protein in yeast strongly impaired growth rate. Analysis of respiration of total recombinant yeast or yeast spheroplasts and in particular of the relationship between respiratory rate and membrane potential of yeast spheroplasts revealed a marked uncoupling activity of respiration, suggesting that although BMCP1 sequence is more distant from the uncoupling proteins (UCPs), this protein could be a fourth member of the UCP family.

Highlights

UCP2 mRNA is widely expressed in animal or human tissues [3, 5,6,7,8], whereas UCP3 mRNA is largely found in skeletal muscle (6 – 8)
The predicted sequence of this protein is less homologous to UCP1, UCP2, or UCP3, the functional analysis of the protein when expressed in yeast indicated its potential uncoupling activity and suggested that it could be a fourth member of the uncoupling proteins (UCPs) family
The screening led to the cloning of a mouse cDNA referred to here as BMCP1

Summary

Introduction

Previous Northern analysis of rodent brain RNA using UCP1 cDNA or UCP2 cDNA suggested the existence of another mRNA related to the family of uncoupling proteins.2 Here, we report the cloning and functional characterization of BMCP1, a novel member of the mitochondrial carrier family that appears to be expressed in brain and, to a lesser extent, in other tissues. The predicted sequence of this protein is less homologous to UCP1, UCP2, or UCP3, the functional analysis of the protein when expressed in yeast indicated its potential uncoupling activity and suggested that it could be a fourth member of the UCP family.

Results

Conclusion