title: Overexpression of the human 2-oxoglutarate carrier lowers mitochondrial membrane potential in HEK-293 cells: contrast with the unique cold-induced mitochondrial carrier CGI-69.
abstract: Using differential mRNA expression analysis, a previously uncharacterized gene was found to be up-regulated 2-fold in brown adipose tissue (BAT) of mice exposed to cold (4 degrees C) for 48 h. Contig and homology analysis revealed that the gene represents the murine orthologue to a sequence from a public database encoding a putative human protein (CGI-69). The presence of mitochondrial carrier domains in the human protein, its transmembrane topology and cold-induction of the mouse CGI-69 gene in BAT prompted an analysis of the idea that CGI-69 may represent a new uncoupling protein (UCP) functional homologue. However, transfection of human CGI-69 isoforms in HEK-293 cells yielded no change in mitochondrial membrane potential (Deltapsi(m)), despite localization of FLAG-tagged CGI-69 to mitochondria of MCF7 cells. Surprisingly, overexpression of the human 2-oxoglutarate carrier (OGC) protein (originally designed as a negative control) sparked a significant drop in Deltapsi(m), possibly signalling a previously unappreciated uncoupling activity for the OGC.
authors.affiliation: Department of Endocrinology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: X X
authors.initials: XX
authors.lastname: Yu
authors.forename: D A
authors.initials: DA
authors.lastname: Lewin
authors.forename: A
authors.initials: A
authors.lastname: Zhong
authors.forename: J
authors.initials: J
authors.lastname: Brush
authors.forename: P W
authors.initials: PW
authors.lastname: Schow
authors.forename: S W
authors.initials: SW
authors.lastname: Sherwood
authors.forename: G
authors.initials: G
authors.lastname: Pan
authors.forename: S H
authors.initials: SH
authors.lastname: Adams
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D003080:Cold Temperature; D007425:Intracellular Membranes / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000096:biosynthesis*; D026901:Membrane Transport Proteins; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D051381:Rats; D011993:Recombinant Fusion Proteins; D017386:Sequence Homology, Amino Acid
chemical_list: C486023:CGI-69 protein, mouse; D002352:Carrier Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011993:Recombinant Fusion Proteins; C422262:SLC25A39 protein, human; C021723:oxoglutarate translocator