tailieunhanh - Báo cáo khoa học: Mitochondrial biogenesis in mtDNA-depleted cells involves a Ca2+-dependent pathway and a reduced mitochondrial protein import

Alterations in mitochondrial activity resulting from defects in mitochond-rial DNA (mtDNA) can modulate the biogenesis of mitochondria by mech-anisms that are still poorly understood. In order to study mitochondrial biogenesis in cells with impaired mitochondrial activity, we used rho-L929 and rho 0 143 B cells (partially and totally depleted of mtDNA, respectively), | ềFEBS Journal Mitochondrial biogenesis in mtDNA-depleted cells involves a Ca2 -dependent pathway and a reduced mitochondrial protein import Ludovic Mercy Aurelia de Pauw Laetitia Payen Silvia Tejerina Andree Houbion Catherine Demazy Martine Raes Patricia Renard and Thierry Arnould Laboratory of Biochemistry and Cellular Biology University of Namur FUNDP Namur Belgium Keywords biogenesis calcium CaMKIV gene expression mitochondrialdysfunction protein import Correspondence T. Arnould Laboratory of Biochemistry and Cellular Biology University of Namur . 61 rue de Bruxelles 5000 Namur Belgium Fax 32 81 724135 Tel 32 81 724321 E-mail Received 31 May 2005 revised 3 August 2005 accepted 11 August 2005 doi Alterations in mitochondrial activity resulting from defects in mitochondrial DNA mtDNA can modulate the biogenesis of mitochondria by mechanisms that are still poorly understood. In order to study mitochondrial biogenesis in cells with impaired mitochondrial activity we used rho-L929 and rho0143 B cells partially and totally depleted of mtDNA respectively that maintain and even up-regulate mitochondrial population to characterize the activity of major transcriptional regulators Sp1 YY1 MEF2 PPARgamma NRF-1 NRF-2 CREB and PGC-1a known to control the expression of numerous nuclear genes encoding mitochondrial proteins. Among these regulators cyclic AMP-responsive element binding protein CREB activity was the only one to be increased in mtDNA-depleted cells. CREB activation mediated by a calcium-dependent pathway in these cells also regulates the expression of cytochrome c and the abundance of mitochondrial population as both are decreased in mtDNA-depleted cells that over-express CREB dominant negative mutants. Mitochondrial biogenesis in mtDNA-depleted cells is also dependent on intracellular calcium as its chelation reduces mitochondrial mass. Despite a slight increase in mitochondrial mass in .