Bonawitz Nicholas D, Chatenay-Lapointe Marc, Pan Yong, Shadel Gerald S
Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA.
Cell Metab. 2007 Apr;5(4):265-77. doi: 10.1016/j.cmet.2007.02.009.
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, wild-type 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.
线粒体呼吸、活性氧（ROS）与寿命之间的关系复杂且仍存在争议。雷帕霉素靶蛋白（TOR）信号通路的抑制可延长多种模式生物的寿命。我们在此表明，TOR1基因的缺失可延长酿酒酵母的时序寿命，主要是通过增强线粒体DNA编码的氧化磷酸化复合体亚基的翻译来增加线粒体呼吸。与先前报道的调节时序寿命的途径不同，我们证明TOR1的缺失可独立于抗氧化基因SOD2延缓衰老。此外，只有在呼吸功能正常且在葡萄糖存在下于常氧环境中生长时，野生型和tor1缺失菌株的寿命才会有所不同。我们提出，TOR信号的抑制会导致在葡萄糖生长过程中呼吸抑制解除，随后线粒体氧消耗的增加会限制糖酵解生长过程中细胞内的氧气和ROS介导的损伤，从而导致细胞内ROS水平降低及时序寿命延长。
