TRANSCRIPTION OF THE MITOCHONDRIAL CITRATE CARRIER GENE: ROLE OF SREBP-1, UPREGULATION BY INSULIN AND DOWNREGULATION BY PUFA

In this study we investigated the transcriptional role of the sterol regulatory element (SRE) present in the promoter of the mitochon- drial citrate carrier (CIC). We show that wild-type (but not mutated) CIC SRE cloned in front of the luciferase promoter confers tran- scriptional activation of the gene reporter. We also demonstrate that insulin activates, and polyunsaturated fatty acids (PUFA) inhibit, the gene reporter activity driven by the CIC promoter containing wild-type (but not mutated) SRE. Finally, both insulin treatment and overexpression of SRE binding protein (SREBP-1) increase the CIC transcript and protein levels, whereas PUFA have an opposite effect. These results show that SRE/SREBP-1 play a role in the transcriptional regulation of CIC by insulin and PUFA.