Biochemical Journal

Research article

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

Xing Xian YU, David A. LEWIN, Alan ZHONG, Jennifer BRUSH, Peter W. SCHOW, Steven W. SHERWOOD, Guohua PAN, Sean H. ADAMS


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°C) for 48h. 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 (∆Ψm), 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 ∆Ψm, possibly signalling a previously unappreciated uncoupling activity for the OGC.

  • metabolic rate
  • oxidative phosphorylation
  • reactive oxygen species
  • respiration
  • thermogenesis