Reduced TOR signaling extends chronological life span via increased respiration and upregulation of mitochondrial gene expression
Reduced TOR signaling extends chronological life span via increased respiration and upregulation of mitochondrial gene expression
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DOI：
10.1016/j.cmet.2007.02.009
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发表时间：
2007-04-01
期刊：
影响因子：
29
通讯作者：
Shadel, Gerald S.
中科院分区：
文献类型：
--
作者：
Bonawitz, Nicholas D.;Chatenay-Lapointe, Marc;Shadel, Gerald S.
线粒体呼吸、活性氧（ROS）和寿命之间的关系是复杂的，仍然存在争议。抑制雷帕霉素靶点（TOR）信号通路延长了几种模式生物的寿命。我们在这里表明，删除TOR1基因延长了酿酒酵母的时间寿命，主要是通过增强线粒体DNA编码的氧化磷酸化复合物亚基的翻译增加线粒体呼吸。与以前报道的调节时序寿命的途径不同，我们证明了TOR1的缺失独立于抗氧化基因SOD2的延缓衰老。此外，野生型和tor1无效株的寿命不同，只有当呼吸能力和生长在常氧葡萄糖的存在下。我们认为，抑制TOR信号导致呼吸抑制在葡萄糖生长过程中，随后增加线粒体耗氧量限制细胞内氧和ROS介导的损害糖酵解生长过程中，导致较低的细胞活性氧和时间寿命的延长。
The relationships between mitochondrial respiration, reactive oxygen species (ROS), and life span are complex and remain controversial. Inhibition of the target of rapamycin (TOR) signaling pathway extends life span in several model organisms. We show here that deletion of the TOR1 gene extends chronological life span in Saccharomyces cerevisiae, primarily by increasing mitochondrial respiration via enhanced translation of mtDNA-encoded oxidative phosphorylation complex subunits. Unlike previously reported pathways regulating chronological life span, we demonstrate that deletion of TOR1 delays aging independently of the antioxidant gene SOD2. Furthermore, wildtype and tor1 null strains differ in life span only when respiration competent and grown in normoxia in the presence of glucose. We propose that inhibition of TOR signaling causes derepression of respiration during growth in glucose and that the subsequent increase in mitochondrial oxygen consumption limits intracellular oxygen and ROS-mediated damage during glycolytic growth, leading to lower cellular ROS and extension of chronological life span.