Alteration of mitochondrial DNA and RNA level in human fibroblasts with impaired vitamin B12 coenzyme synthesis

FEBS Letters

Fracasso, Flavio²  Petruzzella, Vittoria²  Papadia, Francesco³  Gadaleta, Maria Nicola²  Nicoletti, Cinzia²  Cantatore, Palmiro²  Rustin, Pierre¹ 

[1] Unité de Recherches sur les Handicaps Génétiques de l'Enfant INSERM U393, Départment de Génétique and Département de Pédiatrie, Hôpital Necker-Enfants Malades, 149 rue de Sevres, 75743 Paris Cedex 15, France;Department of Biochemistry and Molecular Biology, University of Bari and Centro Studi sui Mitocondri e Metabolismo Energetico, CNR, via Orabona 4A, 70126 Bari, Italy;Divisione Malattie Metaboliche e Genetiche, Azienda Ospedaliera Di Venere-Giovanni XXIII, Bari, Italy

关键词: Methylmalonic aciduria;    Mitochondrial RNA;    Mitochondrial DNA;    Human fibroblast;    Cobalamin coenzyme;    mt;    mitochondrial;    Cbl;    cobalamin;    MeCbl;    methylcobalamin;    AdoCbl;    adenosylcobalamin;    MCM;    methylmalonyl-CoA mutase;    MMA;    methylmalonic aciduria;    Hcys;    homocystinuria;    HCCL;    hydroxycobalamin[c-lactam];   

DOI  :  10.1016/S0014-5793(98)00857-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Alterations of mitochondrial (mt) nucleic acid metabolism in methylmalonic aciduria (MMA) were studied in two cell lines from skin fibroblasts of patients with mitochondrial (GM00595) or cytosolic (GM10011) defects in the biosynthesis pathways of cobalamin coenzymes. The mtDNA level increased two-fold in GM00595 cells, which carry a mt defect in the adenosylcobalamin synthesis, whereas no appreciable change was found in GM10011 cells. The content of the two rRNAs 16S and 12S mtRNAs, normalized for the mtDNA copy number, decreased by 70% and 50% in GM00595 and GM10011, respectively. The normalized content of ND1, ND2 and CO I mRNAs decreased in GM00595, but was unchanged in GM10011. Respiratory chain complex activities measured in these two cell lines were not different from control activities. These data suggest that the maintenance of the mt function is due to doubling of mtDNA and that this compensatory response takes place only in those cells in which the greater reduction of the level of rRNA might have brought the content of these transcripts below the threshold value for optimal expression of the mt genome.

【 授权许可】

Unknown