Mitochondrial gene expression in mammalian striated muscle. Evidence that variation in gene dosage is the major regulatory event.

Mitochondrial gene expression in mammalian striated muscle. Evidence that variation in gene dosage is the major regulatory event.
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DOI:
10.1016/s0021-9258(18)67252-7
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发表时间:
1986-09
期刊:
The Journal of biological chemistry
影响因子:
--
通讯作者:
R. Williams
R. Williams
中科院分区:
其他
文献类型:
--
作者:
R. Williams

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哺乳动物横纹肌的氧化能力可以在近10倍的范围内显著变化,反映出编码氧化代谢酶的基因表达的重大差异,包括专门位于线粒体DNA内的基因。为了阐明线粒体基因在横纹肌中表达的调控事件,利用以线粒体DNA克隆片段为探针的核酸杂交技术,测定了氧化能力明显不同的兔横纹肌中线粒体DNA、线粒体核糖体RNA和细胞色素b基因产物的浓度。当将心肌和I型(红色,氧化)骨骼肌与II型(白色,糖酵解)骨骼肌进行比较时,线粒体DNA、线粒体核糖体RNA和细胞色素b mRNA都与氧化能力的增加成正比。此外,当在体电刺激改变II型骨骼肌的表型特征时,线粒体DNA、线粒体rRNA和细胞色素b mRNA也随着氧化能力的增加而成比例地增加。这些结果表明,哺乳动物横纹肌中线粒体基因的表达与其拷贝数成正比,支持了线粒体基因组相对于染色体DNA的扩增是高度氧化组织中线粒体基因表达增强的重要特征的假说。
The oxidative capacity of mammalian striated muscles can vary markedly over a nearly 10-fold range, reflecting major differences in the expression of genes that encode enzymes of oxidative metabolism, including genes located exclusively within mitochondrial DNA. To clarify the regulatory events that govern expression of mitochondrial genes in striated muscle, nucleic acid hybridization procedures employing cloned segments of mitochondrial DNA as probes were utilized to determine the concentrations of mitochondrial DNA, mitochondrial ribosomal RNA, and cytochrome b mRNA (a mitochondrial gene product) in rabbit striated muscles of markedly different oxidative capacities. When cardiac muscle and Type I (red, oxidative) skeletal muscle were compared to Type II (white, glycolytic) skeletal muscle, mitochondrial DNA, mitochondrial ribosomal RNA, and cytochrome b mRNA, each increased in direct proportion to increases in oxidative capacity. Furthermore, when the phenotypic characteristics of Type II skeletal muscle were altered by electrical stimulation in vivo, mitochondrial DNA, mitochondrial rRNA, and cytochrome b mRNA also increased proportionately with increases in oxidative capacity. These results indicate that the expression of mitochondrial genes in mammalian striated muscle is proportionate to their copy number, and support the hypothesis that amplification of the mitochondrial genome relative to chromosomal DNA is an important feature underlying enhanced expression of mitochondrial genes in highly oxidative tissues.