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

Using differential mRNA expression analysis, a previously uncharacterized g ene was found to be up-regulated-fold in brown adipose tissue (BAT) of mice exposed to cold (4 degreesC) for 48 h. Contig and homology analysis reveal ed that the gene represents the murine orthologue to a sequence from a publ ic database encoding a putative human protein (CGI-69). The presence of mit ochondrial 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) function al homologue, However, transfection of human CGI-69 isoforms in HEK-293 cel ls yielded no change in mitochondrial membrane potential (Delta Psi (m)), d espite localization of FLAG-tagged CGI-69 to mitochondria of MCF7 cells. Su rprisingly, overexpression of the human 2-oxoglutarate carrier (OGC) protei n (originally designed as a negative control) sparked a significant drop in Delta Psi (m), possibly signalling a previously unappreciated uncoupling a ctivity for the OGC.