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 mitochondrial citrate carrier (CIC). We show that wild-type (but not mutated) CIC SRE cloned in front of the luciferase promoter confers transcriptional 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.
Infantino
Vittoria
V
Department of Pharmaco-Biology, Laboratory of Biochemistry and Molecular Biology, University of Bari, Bari, Italy.
Iacobazzi
Vito
V
De Santis
Francesco
F
Mastrapasqua
Mariangela
M
Palmieri
Ferdinando
F
D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D024202:Electrophoretic Mobility Shift Assay; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D009154:Mutation; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism* / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects
D002352:Carrier Proteins; D002867:Chromones; D005231:Fatty Acids, Unsaturated; D007328:Insulin; D024101:Mitochondrial Proteins; D009025:Morpholines; D009841:Oligonucleotides; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; C020723:citrate-binding transport protein; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D008156:Luciferases