Mitochondrial expression and function of GAS-1 in Caenorhabditis elegans

Mitochondrial expression and function of GAS-1 in Caenorhabditis elegans
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DOI:
10.1074/jbc.m011066200
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发表时间:
2001-06-08
影响因子:
4.8
通讯作者:
Sedensky, MM
Sedensky, MM
中科院分区:
生物学2区
文献类型:
--
作者:
Kayser, EB;Morgan, PG;Sedensky, MM

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GAS-1基因的突变改变了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在线虫神经肌肉系统中广泛表达,并以与线粒体蛋白一致的亚细胞模式表达。药理学研究表明,GAS-1部分通过突触前效应发挥作用。此外,根据氧化磷酸化和电子传递的速度来衡量,GAS-1基因的突变大大降低了线粒体中复杂的依赖于i的代谢。在GAS-1动物的线粒体中,也可以看到复杂的II依赖代谢的增加。与野生型相比,GAS-1线虫线粒体的物理结构没有明显的变化。这些数据表明,GAS-1是线虫复合体I的主要49 kDa蛋白质,并且GAS-1蛋白对线虫的线粒体功能至关重要。他们还揭示了线粒体功能的重要性,不仅决定了衰老和寿命,而且还决定了这种模式生物的麻醉敏感性。
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.