Kayser E B, Morgan P G, Hoppel C L, Sedensky M M
Department of Anesthesiology, University Hospitals, Case Western Reserve University, Cleveland, Ohio 44106, USA.
J Biol Chem. 2001 Jun 8;276(23):20551-8. doi: 10.1074/jbc.M011066200. Epub 2001 Feb 20.
A mutation in the gene gas-1 alters sensitivity to volatile anesthetics, fecundity, and life span in the nematode Caenorhabditis elegans. gas-1 encodes a close homologue of the 49-kDa iron protein subunit of Complex I of the mitochondrial electron transport chain from bovine heart. gas-1 is widely expressed in the nematode neuromuscular system and in a subcellular pattern consistent with that of a mitochondrial protein. Pharmacological studies indicate that gas-1 functions partially via presynaptic effects. In addition, a mutation in the gas-1 gene profoundly decreases Complex I-dependent metabolism in mitochondria as measured by rates of both oxidative phosphorylation and electron transport. An increase in Complex II-dependent metabolism also is seen in mitochondria from gas-1 animals. There is no apparent alteration in physical structure in mitochondria from gas-1 nematodes compared with those from wild type. These data indicate that gas-1 is the major 49-kDa protein of complex I and that the GAS-1 protein is critical to mitochondrial function in C. elegans. They also reveal the importance of mitochondrial function in determining not only aging and life span, but also anesthetic sensitivity, in this model organism.
基因gas-1的突变会改变秀丽隐杆线虫对挥发性麻醉剂的敏感性、繁殖力和寿命。gas-1编码牛心脏线粒体电子传递链复合体I的49-kDa铁蛋白亚基的紧密同源物。gas-1在该线虫的神经肌肉系统中广泛表达，且其亚细胞分布模式与线粒体蛋白一致。药理学研究表明，gas-1部分通过突触前效应发挥作用。此外，通过氧化磷酸化和电子传递速率测量发现，gas-1基因突变会显著降低线粒体中复合体I依赖的代谢。在gas-1动物的线粒体中也观察到复合体II依赖的代谢增加。与野生型线虫的线粒体相比，gas-1线虫的线粒体物理结构没有明显变化。这些数据表明，gas-1是复合体I的主要49-kDa蛋白，并且GAS-1蛋白对秀丽隐杆线虫的线粒体功能至关重要。它们还揭示了在这种模式生物中，线粒体功能不仅在决定衰老和寿命方面，而且在决定麻醉敏感性方面都具有重要意义。
