Résumé :
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Communication n° 15. Mitochondria possess its own circular double strand DNA (mtDNA) that is present in multiple copies in mammalian cells. However, this number can vary according to the nature and to the steady state of studied tissues[1,2]. In our study, we investigated the influence of a decrease in mtDNA content on mitochondrial respiratory rate, ATP production and the enzymatic activities of various mitochondrial respiratory chain complexes. We also investigated for the possible existence of a threshold effect in the number of mtDNA copies on mitochondrial energy metabolism by using a set of lymphoblastoïd cell lines harboring various degrees of mtDNA depletion, obtained by ddC treatment and sub-cloning [3]. We observed that mtDNA depletion causes an almost proportional reduction of the activities of the various respiratory chain complexes, as well as of the respiration and ATP synthesis. These results show that there is no threshold in the number of mtDNA copy on the mitochondrial energetic metabolism, and that mtDNA amount in the cell seems to be one of the critical parameters for OXPHOS regulation. In contrast to what is generally observed for OXPHOS complexes inhibition [4], mtDNA does not exist in excess amount that might have been required for compensatory mechanisms. References: [1] Bogenhagen D., and Clayton D.A. (1974) J. Biol. Chem. 249:7991-7995. [2] King M.P., and Attardi G. (1989) Science 246: 500-504. [3] Nelson, I., M.G. Hanna, N.W. Wood and A.E. Harding (1997) Somat Cell Mol Genet 23(4): 287-90. [4] Rossignol, R., M. Malgat, J.P. Mazat and T. Letellier (1999) J Biol Chem 274(47): 33426-32. Key Words: Mitochondria, mtDNA depletion, OXPHOS
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