Abstract |
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.
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Authors | Frédérique Savagner, Delphine Mirebeau, Caroline Jacques, Serge Guyetant, Catherine Morgan, Brigitte Franc, Pascal Reynier, Yves Malthièry |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 310
Issue 3
Pg. 779-84
(Oct 24 2003)
ISSN: 0006-291X [Print] United States |
PMID | 14550271
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- DNA, Complementary
- DNA, Mitochondrial
- DNA-Binding Proteins
- Mitochondrial Proteins
- NF-E2-Related Factor 1
- NRF1 protein, human
- Nuclear Proteins
- Nuclear Respiratory Factor 1
- Nuclear Respiratory Factors
- TFAM protein, human
- Trans-Activators
- Transcription Factors
- mitochondrial transcription factor A
- peroxisome-proliferator-activated receptor-gamma coactivator-1
- Electron Transport Complex IV
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Topics |
- Adenoma
(metabolism)
- Adenoma, Oxyphilic
(metabolism)
- Carcinoma
(metabolism)
- Cell Division
- Cell Nucleus
(metabolism)
- DNA, Complementary
(metabolism)
- DNA, Mitochondrial
(metabolism)
- DNA-Binding Proteins
(biosynthesis)
- Electron Transport Complex IV
(metabolism)
- Humans
- Mitochondria
(metabolism)
- Mitochondrial Proteins
- Models, Biological
- NF-E2-Related Factor 1
- Nuclear Proteins
(biosynthesis)
- Nuclear Respiratory Factor 1
- Nuclear Respiratory Factors
- Polymerase Chain Reaction
- Protein Structure, Tertiary
- Thyroid Neoplasms
(metabolism)
- Trans-Activators
(biosynthesis)
- Transcription Factors
(biosynthesis)
- Up-Regulation
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