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Nitric Oxide and Calcium Participate in the Fine Regulation of Mitochondrial Biogenesis in Follicular Thyroid Carcinoma Cells

Abstract :

Members of the peroxisome proliferator-activated receptor γ coactivator-1 family (i.e. PGC-1α, PGC-1β, and the PGC-1-related coactivator (PRC)) are key regulators of mitochondrial biogenesis and function. These regulators serve as mediators between environmental or endogenous signals and the transcriptional machinery governing mitochondrial biogenesis. The FTC-133 and RO82 W-1 follicular thyroid carcinoma cell lines, which present significantly different numbers of mitochondria, metabolic mechanisms, and expression levels of PRC and PGC-1α, may employ retrograde signaling in response to respiratory dysfunction. Nitric oxide (NO) and calcium have been hypothesized to participate in this activity. We investigated the effects of the S-nitroso-N-acetyl-dl-penicillamine-NO donor, on the expression of genes involved in mitochondrial biogenesis and cellular metabolic functions in FTC-133 and RO82 W-1 cells by measuring lactate dehydrogenase and cytochrome c oxidase (COX) activities. We studied the action of ionomycin and 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid-acetoxymethyl ester (BAPTA/AM) (i.e. a calcium ionophore and a cytosolic calcium chelator) on whole genome expression and mitochondrial biogenesis in RO82 W-1 cells. COX activity and the dynamics of endoplasmic reticulum and mitochondrial networks were analyzed in regard to calcium-modulating treatments. In the FTC-133 and RO82 W-1 cells, the mitochondrial biogenesis induced by NO was mainly related to PRC expression as a retrograde mitochondrial signaling. Ionomycin diminished COX activity and negatively regulated PRC-mediated mitochondrial biogenesis in RO82 W-1 cells, whereas BAPTA/AM produced the opposite effects with a reorganization of the mitochondrial network. This is the first demonstration that NO and calcium regulate mitochondrial biogenesis through the PRC pathway in thyroid cell lines.

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Soumis le : jeudi 1 juillet 2021 - 12:38:31
Dernière modification le : lundi 14 novembre 2022 - 01:32:05

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Soazig Le Pennec, Delphine Mirebeau-Prunier, Nathalie Bouzamondo, Caroline Jacques, Delphine Guillotin, et al.. Nitric Oxide and Calcium Participate in the Fine Regulation of Mitochondrial Biogenesis in Follicular Thyroid Carcinoma Cells. Journal of Biological Chemistry, 2011, 286 (20), pp.18229 - 18239. ⟨10.1074/jbc.M110.217521⟩. ⟨hal-03275686⟩



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