Kayser Ernst-Bernhard, Sedensky Margaret M, Morgan Phil G
Department of Anesthesiology, University Hospitals and Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5007, USA.
Mech Ageing Dev. 2004 Jun;125(6):455-64. doi: 10.1016/j.mad.2004.04.002.
A mutation in a subunit of complex I of the mitochondrial electron transport chain (gas-1) causes Caenorhabditis elegans to be hypersensitive to volatile anesthetics and oxygen as well as shortening lifespan. We hypothesized that changes in mitochondrial respiration or reactive oxygen species production cause these changes. Therefore, we compared gas-1 to other mitochondrial mutants to identify the relative importance of these two aspects of mitochondrial function in determining longevity. Lifespans of gas-1 and mev-1 were decreased compared with N2, while that of clk-1 was increased. Rates of oxidative phosphorylation were decreased in all three mutants, but the ROS damage was decreased only in clk-1. Suppressors of gas-1 increased rates of oxidative phosphorylation, decreased oxidative damage to mitochondrial proteins and increased lifespan. Two strains containing combinations of mutations predicted to have very decreased complex I function, had unexpectedly long lifespans. We conclude that mitochondrial changes in lifespan appear to be mediated primarily by changes in oxidative damage rather than by changes in rates of oxidative phosphorylation. In contrast, the effects of mitochondrial changes on anesthetic sensitivity appear to be mediated by both altered respiration and oxidative damage.
线粒体电子传递链复合体I（gas-1）的一个亚基发生突变，会导致秀丽隐杆线虫对挥发性麻醉剂和氧气高度敏感，并缩短其寿命。我们推测线粒体呼吸或活性氧产生的变化会导致这些改变。因此，我们将gas-1与其他线粒体突变体进行比较，以确定线粒体功能的这两个方面在决定寿命方面的相对重要性。与N2相比，gas-1和mev-1的寿命缩短，而clk-1的寿命延长。所有三个突变体的氧化磷酸化速率均降低，但只有clk-1的活性氧损伤降低。gas-1的抑制子提高了氧化磷酸化速率，降低了线粒体蛋白的氧化损伤，并延长了寿命。两个含有预计会使复合体I功能大幅下降的突变组合的品系，其寿命却出人意料地长。我们得出结论，线粒体寿命的变化似乎主要由氧化损伤的变化介导，而非氧化磷酸化速率的变化。相比之下，线粒体变化对麻醉敏感性的影响似乎由呼吸改变和氧化损伤共同介导。
Zotero 插件