Research Article: PGC-1-Related Coactivator Modulates Mitochondrial-Nuclear Crosstalk through Endogenous Nitric Oxide in a Cellular Model of Oncocytic Thyroid Tumours

Date Published: November 23, 2009

Publisher: Public Library of Science

Author(s): Mahatsangy Raharijaona, Soazig Le Pennec, Julie Poirier, Delphine Mirebeau-Prunier, Clothilde Rouxel, Caroline Jacques, Jean-Fred Fontaine, Yves Malthiery, Rémi Houlgatte, Frédérique Savagner, Thomas Preiss.

Abstract: The PGC-1 related coactivator (PRC), which shares structural and functional features with PGC-1α, is believed to regulate several metabolic pathways as well as mitochondrial biogenesis. Its involvement in the early programming of cell proliferation suggests the existence of finely regulated crosstalk between mitochondrial functions and the cell cycle status.

Partial Text: Several essential cellular functions of mitochondria depend on a high degree of functional interaction between the nuclear and mitochondrial genomes. Of the hundred structural subunits that make up the oxidative phosphorylation (OXPHOS) complexes, 13 are encoded by the mitochondrial genome. The mechanisms governing the coordination of the multiple transcription factors involved in mitochondrial biogenesis have been partly explained by the discovery of the PGC-1 coactivator family [1]. Three members of this family – PGC1α, PGC1β and PRC – regulate several functions, including adaptative thermogenesis, glucidic metabolism, fatty acid oxidation and mitochondrial metabolism, via functional interactions with various transcriptional factors. Mitochondrial biogenesis is controlled by PGC mainly through interactions with nuclear respiratory factors, NRF-1 and NRF-2, and may be induced via p38 mitogen-activated protein kinase. In a cell-selective manner, the efficiency of the oxidative phosphorylation process may also be regulated by PGC through the transcriptional control of uncoupling proteins (UCPs) [2].

PRC, a member of the family of PGC1 transcriptional coactivators, is expressed more abundantly in proliferative cells than in growth-arrested cells. Several studies have demonstrated the important role played by these coactivators in modulating tissue energetic resources [22]. In the mitochondrial-rich tumour model we investigated, PGC-1α expression remained very low, being induced neither by serum nor in compensation to PRC repression.



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