Downregulation of Tfam and mtDNA copy number during mammalian spermatogenesis

Downregulation of Tfam and mtDNA copy number during mammalian spermatogenesis
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DOI:
10.1007/s00335-001-2052-8
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发表时间:
2001-10-01
期刊:
影响因子:
2.5
通讯作者:
Larsson, NG
Larsson, NG
中科院分区:
生物学4区
文献类型:
--
作者:
Rantanen, A;Jansson, M;Larsson, NG

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线粒体转录因子A (Mitochondrial transcription factor A, Tfam)是mtDNA维持所必需的,线粒体Tfam蛋白水平直接影响mtDNA拷贝数。先前的研究表明,在小鼠和男性精子发生过程中,线粒体中Tfam蛋白水平显著降低,同时出现大量睾丸特异性Tfam mRNA亚型。有趣的是,在小鼠中发现了大量功能未知的睾丸特异性核Tfam蛋白异构体,但在人类中却没有。我们现在已经确定了Tfam在大鼠睾丸中的表达,以确定哺乳动物精子发生的保守特征。核Tfam蛋白异构体在大鼠中不存在,因此在哺乳动物精子发生中是必不可少的。与小鼠和人类相似,我们发现在大鼠精子发生过程中,线粒体Tfam蛋白水平下调,替代Tfam转录本表达,mtDNA拷贝数下调。因此,这些特征对所有哺乳动物都是共同的,可能提供了阻止父系mtDNA传播的几种机制之一。
Mitochondrial transcription factor A (Tfam) is required for mtDNA maintenance, and mitochondrial Tfam protein levels directly affect mtDNA copy number. Previous studies have shown significant reduction of Tfam protein levels in mitochondria together with the appearance of abundant testis-specific Tfam mRNA isoforms as spermatogenesis proceeds in both mouse and man. Interestingly, an abundant testis-specific nuclear Tfam protein isoform of unknown function is found in the mouse, but not in humans. We have now characterized Tfam expression in rat testis to identify conserved features in mammalian spermatogenesis. The nuclear Tfam protein isoform, is absent in the rat and is thus dispensable for mammalian spermatogenesis. Similar to mice and humans, we found expression of alternate Tfam transcripts, downregulation of mitochondrial Tfam protein levels, and downregulation of mtDNA copy number during rat spermatogenesis. These features are thus common to all mammals and may provide one of several mechanisms preventing paternal mtDNA transmission.