Koga Y, Davidson M, Schon E A, King M P
Department of Neurology, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
Muscle Nerve Suppl. 1995;3:S119-23. doi: 10.1002/mus.880181424.
MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes), a maternally inherited mitochondrial disorder, has been associated with an A-->G transition at nucleotide 3243 and a T-->C transition at nucleotide 3271, both in the mitochondrial tRNA(Leu(UUR)) gene. We transferred mitochondria harboring these mutations into human cells lacking endogenous mtDNA (rho o cells), and analyzed the resulting transmitochondrial cytoplasmic hybrid (cybrid) cell lines for the relationship of genotype to phenotype. Cybrids containing high levels of mutated genomes showed decreased rates of synthesis of mitochondrial translation products, reduced respiratory chain function, and increased amounts of a novel unprocessed RNA species (RNA 19). Overall effects on mitochondrial functions were more severe for the MELAS 3243 cybrids as compared to the MELAS 3271 cybrids. These data, combined with our previous observations, suggest that RNA 19 may play an important, but as yet uncharacterized, role in the pathogenesis of this mitochondrial disorder.
线粒体肌病、脑病、乳酸酸中毒和卒中样发作（MELAS）是一种母系遗传的线粒体疾病，与线粒体tRNA（Leu（UUR））基因中第3243位核苷酸由A向G的转变以及第3271位核苷酸由T向C的转变有关。我们将携带这些突变的线粒体导入缺乏内源性线粒体DNA的人类细胞（ρ⁰细胞），并分析由此产生的线粒体细胞质杂交（细胞融合体）细胞系中基因型与表型的关系。含有高水平突变基因组的细胞融合体显示线粒体翻译产物的合成速率降低、呼吸链功能减弱以及一种新的未加工RNA种类（RNA 19）的量增加。与MELAS 3271细胞融合体相比，MELAS 3243细胞融合体对线粒体功能的总体影响更严重。这些数据与我们之前的观察结果相结合，表明RNA 19可能在这种线粒体疾病的发病机制中起重要作用，但尚未明确其特征。
