Tsang William Y, Lemire Bernard D
Canadian Institutes of Health Research Group in the Molecular Biology of Membrane Proteins, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada.
Biochem Biophys Res Commun. 2002 Feb 15;291(1):8-16. doi: 10.1006/bbrc.2002.6394.
Growth and development rely on the mitochondrial respiratory chain (MRC) as the major source of ATP. We measured the mitochondrial DNA (mtDNA) copy number of each of the Caenorhabditis elegans developmental stages. Embryos, L1, L2, and L3 larvae all have approximately 25,000 copies of maternally derived mtDNA. The copy number increases fivefold in L4 larvae and a further sixfold in adult hermaphrodites, but only twofold in adult males. The majority of mtDNA in adult worms is germline associated, and germline-deficient mutants show markedly reduced mtDNA contents. With sperm-deficient or oocyte-deficient mutants, we confirm that mtDNA amplification is primarily associated with oocyte production. When mtDNA replication is inhibited, a quantitative and homogeneous arrest as L3 larvae occurs. Thus, mtDNA amplification is a necessary component of normal development and its regulation may involve an energy-sensing decision or checkpoint that can be invoked when mitochondrial energy generation is impaired.
生长和发育依赖线粒体呼吸链(MRC)作为ATP的主要来源。我们测量了秀丽隐杆线虫每个发育阶段的线粒体DNA(mtDNA)拷贝数。胚胎、L1、L2和L3幼虫都有大约25,000个母源mtDNA拷贝。拷贝数在L4幼虫中增加五倍,在成年雌雄同体中进一步增加六倍,但在成年雄性中仅增加两倍。成年蠕虫中的大多数mtDNA与生殖系相关,生殖系缺陷型突变体的mtDNA含量明显降低。通过精子缺陷或卵母细胞缺陷型突变体,我们证实mtDNA扩增主要与卵母细胞产生有关。当mtDNA复制受到抑制时,会出现L3幼虫阶段的定量且均匀的停滞。因此,mtDNA扩增是正常发育的必要组成部分,其调控可能涉及能量感应决策或线粒体能量生成受损时可启动的检查点。