Heddi A, Lestienne P, Wallace D C, Stepien G
Centre de Génétique Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Unité Mixte de Recherches 106, Villeurbanne, France.
J Biol Chem. 1993 Jun 5;268(16):12156-63.
The expression of nuclear and mitochondrial oxidative phosphorylation (OXPHOS) genes was examined in the skeletal muscle of patients with Kearns-Sayre syndrome (KSS), myoclonic epilepsy associated with ragged red fibers (MERRF), and myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and compared with controls. In KSS muscle, mtDNA transcripts outside the deletion were elevated, while those within the deletion were reduced according to the percentage of deleted mtDNA molecules. In MERRF and MELAS muscle, mitochondrial transcripts levels were increased, but the increase was greater in MERRF muscle. The processing of mtDNA transcripts was reduced in all pathogenic muscles. This was true for full-length heavy and light strand transcripts as well as for the 16 S rRNA + tRNA(Leu)+ND1 transcript. However, the tRNA(Lys) level was reduced in all three muscles. In MELAS muscle, our results are not consistent with an impairment of transcription termination at the end of the 16 S mitochondrial rRNA. Finally, the transcription of the nuclear ATPsyn.beta and ANT1 genes was induced in parallel with the high level of mtDNA transcripts in MERRF and MELAS muscle, but was repressed in KSS muscle. The results demonstrate that the expression of nuclear and cytoplasmic OXPHOS genes is coordinated and that OXPHOS gene expression increases to compensate for respiratory deficiency. The repression of nuclear genes in KSS muscle could be a consequence of the segmental distribution of deleted mtDNA molecules in muscle cells.
我们检测了患有卡恩斯-塞尔综合征（KSS）、肌阵挛性癫痫伴破碎红纤维（MERRF）以及肌病、脑病、乳酸性酸中毒和卒中样发作（MELAS）患者骨骼肌中核及线粒体氧化磷酸化（OXPHOS）基因的表达，并与对照组进行比较。在KSS患者的肌肉中，缺失区域外的线粒体DNA转录本升高，而缺失区域内的转录本则根据缺失的线粒体DNA分子百分比而减少。在MERRF和MELAS患者的肌肉中，线粒体转录本水平升高，但MERRF患者肌肉中的升高幅度更大。所有致病肌肉中线粒体DNA转录本的加工过程均减少。全长重链和轻链转录本以及16S rRNA + tRNA(Leu)+ND1转录本均是如此。然而，所有三种肌肉中的tRNA(Lys)水平均降低。在MELAS患者的肌肉中，我们的结果与16S线粒体rRNA末端转录终止受损不一致。最后，在MERRF和MELAS患者的肌肉中，核ATPsyn.beta和ANT1基因的转录与高水平的线粒体DNA转录本平行诱导，但在KSS患者的肌肉中受到抑制。结果表明，核及细胞质OXPHOS基因的表达是协调的，并且OXPHOS基因表达增加以补偿呼吸缺陷。KSS患者肌肉中核基因的抑制可能是肌肉细胞中缺失的线粒体DNA分子呈节段性分布的结果。
