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发育和肿瘤发生过程中肝脏中的线粒体生物发生

Mitochondrial biogenesis in the liver during development and oncogenesis.

作者信息

Cuezva J M, Ostronoff L K, Ricart J, López de Heredia M, Di Liegro C M, Izquierdo J M

机构信息

Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Spain.

出版信息

J Bioenerg Biomembr. 1997 Aug;29(4):365-77. doi: 10.1023/a:1022450831360.

DOI:10.1023/a:1022450831360
PMID:9387097
Abstract

The analysis of the expression of oxidative phosphorylation genes in the liver during development reveals the existence of two biological programs involved in the biogenesis of mitochondria. Differentiation is a short-term program of biogenesis that is controlled at post-transcriptional levels of gene expression and is responsible for the rapid changes in the bioenergetic phenotype of mitochondria. In contrast, proliferation is a long-term program controlled both at the transcriptional and post-transcriptional levels of gene expression and is responsible for the increase in mitochondrial mass in the hepatocyte. Recently, a specific subcellular structure involved in the localization and control of the translation of the mRNA encoding the beta-catalytic subunit of the H(+)-ATP synthase (beta-mRNA) has been identified. It is suggested that this structure plays a prominent role in the control of mitochondrial biogenesis at post-transcriptional levels. The fetal liver has many phenotypic manifestations in common with highly glycolytic tumor cells. In addition, both have a low mitochondrial content despite a paradoxical increase in the cellular representation of oxidative phosphorylation transcripts. Based on the paradigm provided by the fetal liver we hypothesize that the aberrant mitochondrial phenotype of fast-growing hepatomas represents a reversion to a fetal program of expression of oxidative phosphorylation genes by the activation, or increased expression, of an inhibitor of beta-mRNA translation.

摘要

对发育过程中肝脏氧化磷酸化基因表达的分析揭示了线粒体生物发生过程中涉及的两种生物学程序。分化是一种短期的生物发生程序,在基因表达的转录后水平受到控制,负责线粒体生物能量学表型的快速变化。相比之下,增殖是一种长期程序,在基因表达的转录和转录后水平均受到控制,负责肝细胞中线粒体质量的增加。最近,一种与编码H(+)-ATP合酶β催化亚基的mRNA(β-mRNA)翻译的定位和控制有关的特定亚细胞结构已被鉴定。有人提出,这种结构在转录后水平的线粒体生物发生控制中起重要作用。胎儿肝脏与高度糖酵解的肿瘤细胞有许多共同的表型表现。此外,尽管氧化磷酸化转录本的细胞表达出现矛盾性增加,但两者的线粒体含量均较低。基于胎儿肝脏提供的范例,我们推测快速生长的肝癌异常线粒体表型代表通过激活β-mRNA翻译抑制剂或增加其表达,向胎儿氧化磷酸化基因表达程序的逆转。

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