BMCP1, a novel mitochondrial carrier with high expression in the central nervous system of humans and rodents, and respiration uncoupling activity in recombinant yeast.
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.
Sanchis
D
D
Centre National de la Recherche Scientifique, Centre de Recherche sur l'Endocrinologie Moléculaire et le Développement, 9 rue Jules Hetzel 92190 Meudon, France.
Fleury
C
C
Chomiki
N
N
Goubern
M
M
Huang
Q
Q
Neverova
M
M
Grégoire
F
F
Easlick
J
J
Raimbault
S
S
Lévi-Meyrueis
C
C
Miroux
B
B
Collins
S
S
Seldin
M
M
Richard
D
D
Warden
C
C
Bouillaud
F
F
Ricquier
D
D
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002874:Chromosome Mapping; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D007425:Intracellular Membranes / Q000502:physiology; D008297:Male; D008564:Membrane Potentials; D026901:Membrane Transport Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D000071245:Mitochondrial Uncoupling Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D009928:Organ Specificity; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014475:Uncoupling Agents; D014960:X Chromosome
D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D000071245:Mitochondrial Uncoupling Proteins; D009419:Nerve Tissue Proteins; C116584:SLC25A14 protein, human; C492124:Slc25a14 protein, mouse; C492125:Slc25a14 protein, rat; D014475:Uncoupling Agents