School of Pharmacy, Kitasato University, Tokyo 108-8641, Japan.
J Biol Chem. 2012 Feb 10;287(7):4590-601. doi: 10.1074/jbc.M111.314823. Epub 2011 Dec 15.
Cardiolipin (CL) is a major membrane phospholipid specifically localized in mitochondria. At the cellular level, CL has been shown to have a role in mitochondrial energy production, mitochondrial membrane dynamics, and the triggering of apoptosis. However, the in vivo role of CL in multicellular organisms is largely unknown. In this study, by analyzing deletion mutants of a CL synthase gene (crls-1) in Caenorhabditis elegans, we demonstrated that CL depletion selectively caused abnormal mitochondrial function and morphology in germ cells but not in somatic cell types such as muscle cells. crls-1 mutants reached adulthood but were sterile with reduced germ cell proliferation and impaired oogenesis. In the gonad of crls-1 mutants, mitochondrial membrane potential was significantly decreased, and the structure of the mitochondrial cristae was disrupted. Contrary to the abnormalities in the gonad, somatic tissues in crls-1 mutants appeared normal with respect to cell proliferation, mitochondrial function, and mitochondrial morphology. Increased susceptibility to CL depletion in germ cells was also observed in mutants of phosphatidylglycerophosphate synthase, an enzyme responsible for producing phosphatidylglycerol, a precursor phospholipid of CL. We propose that the contribution of CL to mitochondrial function and morphology is different among the cell types in C. elegans.
心磷脂 (CL) 是一种主要的膜磷脂，特异性定位于线粒体。在细胞水平上，CL 被证明在线粒体能量产生、线粒体膜动力学和细胞凋亡的触发中发挥作用。然而，CL 在多细胞生物体内的体内作用在很大程度上尚不清楚。在这项研究中，通过分析秀丽隐杆线虫中 CL 合酶基因 (crls-1) 的缺失突变体，我们证明 CL 耗竭选择性地导致生殖细胞中线粒体功能和形态异常，但不会导致肌肉细胞等体细胞类型异常。crls-1 突变体可以达到成年期，但不育，生殖细胞增殖减少，卵子发生受损。在 crls-1 突变体的生殖腺中，线粒体膜电位显著降低，线粒体嵴的结构被破坏。与生殖腺的异常相反，crls-1 突变体的体细胞组织在细胞增殖、线粒体功能和线粒体形态方面似乎正常。负责产生心磷脂前体磷脂酰甘油的磷酸甘油磷酸合酶突变体中也观察到生殖细胞对 CL 耗竭的敏感性增加。我们提出，CL 对秀丽隐杆线虫中不同细胞类型中线粒体功能和形态的贡献是不同的。
