tailieunhanh - Báo cáo khoa học: Estrogen-related receptor a and PGC-1-related coactivator constitute a novel complex mediating the biogenesis of functional mitochondria

Mitochondrial biogenesis, which depends on nuclear as well as mitochon-drial genes, occurs in response to increased cellular ATP demand. The nuclear transcriptional factors, estrogen-related receptor a (ERRa) and nuclear respiratory factors 1 and 2, are associated with the coordination of the transcriptional machinery governing mitochondrial biogenesis | ỊFEBS Journal Estrogen-related receptor a and PGC-1-related coactivator constitute a novel complex mediating the biogenesis of functional mitochondria Delphine Mirebeau-Prunier1-3 Soazig Le Pennec1 2 Caroline Jacques1 2 Naig Gueguen3 Julie Poirier1 2 Yves Malthiery1-3 and Frederique Savagner1-3 1 INSERM UMR694 Angers France 2 Universite d Angers France 3 CHU Angers Laboratoire de Biochimie et Biologie moleculaire France Keywords cell proliferation estrogen-related receptor a mitochondrialbiogenesis PGC-1-related coactivator respiratory chain Correspondence D. Mirebeau-Prunier INSERM UMR 694 CHU 4 rue Larrey 49033 Angers France Fax 33 241 35 40 17 Tel 33 241 35 33 14 E-mail deprunier@ Received 17 September 2009 revised 10 November 2009 accepted 25 November 2009 doi Mitochondrial biogenesis which depends on nuclear as well as mitochondrial genes occurs in response to increased cellular ATP demand. The nuclear transcriptional factors estrogen-related receptor a ERRa and nuclear respiratory factors 1 and 2 are associated with the coordination of the transcriptional machinery governing mitochondrial biogenesis whereas coactivators of the peroxisome proliferator-activated receptor c coactivator-1 PGC-1 family serve as mediators between the environment and this machinery. In the context of proliferating cells PGC-1-related coactivator PRC is a member of the PGC-1 family which is known to act in partnership with nuclear respiratory factors but no functional interference between PRC and ERRa has been described so far. We explored three thyroid cell lines FTC-133 and RO 82 W-1 each characterized by a different mitochondrial content and studied their behavior towards PRC and ERRa in terms of respiratory efficiency. Overexpression of PRC and ERRa led to increased respiratory chain capacity and mitochondrial mass. The inhibition of ERRa decreased cell growth and respiratory chain capacity in all three cell lines. However the

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