Cantatore P, Petruzzella V, Nicoletti C, Papadia F, Fracasso F, Rustin P, Gadaleta M N
Department of Biochemistry and Molecular Biology, University of Bari and Centro Studi sui Mitocondri e Metabolismo Energetico, CNR, Italy.
FEBS Lett. 1998 Aug 7;432(3):173-8. doi: 10.1016/s0014-5793(98)00857-6.
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.
在来自钴胺素辅酶生物合成途径存在线粒体（GM00595）或胞质（GM10011）缺陷患者的皮肤成纤维细胞的两种细胞系中，研究了甲基丙二酸尿症（MMA）中线粒体（mt）核酸代谢的改变。在腺苷钴胺素合成存在mt缺陷的GM00595细胞中，mtDNA水平增加了两倍，而在GM10011细胞中未发现明显变化。以mtDNA拷贝数标准化后，两种rRNA即16S和12S mtRNA的含量在GM00595和GM10011中分别下降了70%和50%。GM00595中ND1、ND2和CO I mRNA的标准化含量下降，但GM10011中未改变。在这两种细胞系中测得的呼吸链复合体活性与对照活性无差异。这些数据表明，mt功能的维持归因于mtDNA的加倍，并且这种补偿反应仅发生在那些rRNA水平大幅降低可能使这些转录本含量低于mt基因组最佳表达阈值的细胞中。
