Bratic Ivana, Hench Jürgen, Henriksson Johan, Antebi Adam, Bürglin Thomas R, Trifunovic Aleksandra
Department of Laboratory Medicine, Division of Metabolic Diseases, Novum, Karolinska Institutet, Stockholm SE-141 86, Sweden.
Nucleic Acids Res. 2009 Apr;37(6):1817-28. doi: 10.1093/nar/gkp018. Epub 2009 Jan 30.
A number of studies showed that the development and the lifespan of Caenorhabditis elegans is dependent on mitochondrial function. In this study, we addressed the role of mitochondrial DNA levels and mtDNA maintenance in development of C. elegans by analyzing deletion mutants for mitochondrial polymerase gamma (polg-1(ok1548)). Surprisingly, even though previous studies in other model organisms showed necessity of polymerase gamma for embryonic development, homozygous polg-1(ok1548) mutants had normal development and reached adulthood without any morphological defects. However, polg-1 deficient animals have a seriously compromised gonadal function as a result of severe mitochondrial depletion, leading to sterility and shortened lifespan. Our results indicate that the gonad is the primary site of mtDNA replication, whilst the mtDNA of adult somatic tissues mainly stems from the developing embryo. Furthermore, we show that the mtDNA copy number shows great plasticity as it can be almost tripled as a response to the environmental stimuli. Finally, we show that the mtDNA copy number is an essential limiting factor for the worm development and therefore, a number of mechanisms set to maintain mtDNA levels exist, ensuring a normal development of C. elegans even in the absence of the mitochondrial replicase.
多项研究表明，秀丽隐杆线虫的发育和寿命取决于线粒体功能。在本研究中，我们通过分析线粒体聚合酶γ（polg-1(ok1548)）的缺失突变体，探讨了线粒体DNA水平和线粒体DNA维持在秀丽隐杆线虫发育中的作用。令人惊讶的是，尽管之前在其他模式生物中的研究表明聚合酶γ对胚胎发育是必需的，但纯合的polg-1(ok1548)突变体发育正常，成年后没有任何形态缺陷。然而，由于严重的线粒体耗竭，polg-1缺陷动物的性腺功能严重受损，导致不育和寿命缩短。我们的结果表明，性腺是线粒体DNA复制的主要部位，而成体体细胞组织的线粒体DNA主要来源于发育中的胚胎。此外，我们表明线粒体DNA拷贝数具有很大的可塑性，因为它可以作为对环境刺激的反应几乎增加两倍。最后，我们表明线粒体DNA拷贝数是线虫发育的一个重要限制因素，因此，存在许多维持线粒体DNA水平的机制，确保即使在没有线粒体复制酶的情况下秀丽隐杆线虫也能正常发育。
