PGC-1-related coactivator and targets are upregulated in thyroid oncocytoma.
Thyroid oncocytomas are tumors characterized by dense mitochondrial accumulation, the cause of which is currently unknown. Members of the PGC-1 coactivator family have been identified as important mediators of mitochondrial biogenesis because of their ability to activate nuclear genes encoding mitochondrial proteins. We have investigated the influence of the PGC-1 related coactivator (PRC) on the high mitochondrial content observed in oncocytoma by quantifying the transcripts of PRC, the nuclear respiratory factor 1 (NRF-1) and the mitochondrial transcription factor A (TFAM), in 30 oncocytic tumors and corresponding normal tissues. The three genes studied were found to be significantly overexpressed in thyroid oncocytomas, concomitantly with an increase in cytochrome oxidase activity and mitochondrial DNA (mtDNA) content. However, no mtDNA variant in the D-loop region appeared to be involved in oncocytic development. We conclude that overexpression of the PRC pathway is responsible for mitochondrial proliferation in the context of thyroid oncocytoma.
Savagner
Frédérique
F
INSERM EMI-U 00-18, Laboratoire de Biochimie et Biologie Moléculaire, CHU, Angers, France. frsavagner@chu-angers.fr
Mirebeau
Delphine
D
Jacques
Caroline
C
Guyetant
Serge
S
Morgan
Catherine
C
Franc
Brigitte
B
Reynier
Pascal
P
Malthièry
Yves
Y
D000236:Adenoma / Q000378:metabolism; D018249:Adenoma, Oxyphilic / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D003576:Electron Transport Complex IV / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins; D008954:Models, Biological; D051265:NF-E2-Related Factor 1; D009687:Nuclear Proteins / Q000096:biosynthesis; D051266:Nuclear Respiratory Factor 1; D051264:Nuclear Respiratory Factors; D016133:Polymerase Chain Reaction; D017434:Protein Structure, Tertiary; D013964:Thyroid Neoplasms / Q000378:metabolism*; D015534:Trans-Activators / Q000096:biosynthesis*; D014157:Transcription Factors / Q000096:biosynthesis; D015854:Up-Regulation
D018076:DNA, Complementary; D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D051265:NF-E2-Related Factor 1; C495633:NRF1 protein, human; D009687:Nuclear Proteins; D051266:Nuclear Respiratory Factor 1; D051264:Nuclear Respiratory Factors; C499631:TFAM protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C422562:mitochondrial transcription factor A; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D003576:Electron Transport Complex IV