title: 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.
authors: INSERM UMR694, Centre Hospitalier Universitaire d’Angers, F-49033 Angers, France.
authors: Soazig
authors: S
authors: Le Pennec
authors: Delphine
authors: D
authors: Mirebeau-Prunier
authors: Nathalie
authors: N
authors: Boutet-Bouzamondo
authors: Caroline
authors: C
authors: Jacques
authors: Delphine
authors: D
authors: Guillotin
authors: Emilie
authors: E
authors: Lauret
authors: Rémi
authors: R
authors: Houlgatte
authors: Yves
authors: Y
authors: Malthièry
authors: Frédérique
authors: F
authors: Savagner
mesh_terms: D018263:Adenocarcinoma, Follicular; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000096:biosynthesis* / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009569:Nitric Oxide / Q000235:genetics / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism
chemical_list: D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D002118:Calcium