Abstract：
N-(1,3-dimethylbutyl)-N\'-phenyl-p-phenylenediamine quinone (6-PPDQ) is an emerging pollutant transformed from 6-PPD. However, the effect of 6-PPDQ exposure on mitochondrion and underlying mechanism remains largely unclear. Using Caenorhabditis elegans as animal model, exposed to 6-PPDQ at 0.1-10 μg/L was performed form L1 larvae to adult day-1. Exposure to 6-PPDQ (1 and 10 μg/L) could increase oxygen consumption rate and decease adenosine 5\'-triphosphate (ATP) content, suggesting induction of mitochondrial dysfunction. Activities of NADH dehydrogenase (complex I) and succinate dehydrogenase (complex II) were inhibited, accompanied by a decrease in expressions of gas-1, nuo-1, and mev-1. RNAi of gas-1 and mev-1 enhanced mitochondrial dysfunction and reduced lifespan of 6-PPDQ exposed nematodes. GAS-1 and MEV-1 functioned in parallel to regulate 6-PPDQ toxicity to reduce the lifespan. Insulin peptides and the insulin signaling pathway acted downstream of GAS-1 and MEV-1 to control the 6-PPDQ toxicity on longevity. Moreover, RNAi of sod-2 and sod-3, targeted genes of daf-16, caused susceptibility to 6-PPDQ toxicity in reducing lifespan and in causing reactive oxygen species (ROS) production. Therefore, 6-PPDQ at environmentally relevant concentrations (ERCs) potentially caused mitochondrial dysfunction by affecting mitochondrial complexes I and II, which was associated with lifespan reduction by affecting insulin signaling in organisms.
摘要：
N-（1,3-二甲基丁基）-N'-苯基-对苯二胺醌（6-PPDQ）是由6-PPD转化而来的新兴污染物。然而,6-PPDQ暴露对线粒体的影响和潜在机制尚不清楚。以秀丽隐杆线虫为动物模型,从L1幼虫到成年第1天，以0.1-10μg/L暴露于6-PPDQ。暴露于6-PPDQ（1和10μg/L）可以增加耗氧率并降低5'-三磷酸腺苷（ATP）含量，提示线粒体功能障碍的诱导。NADH脱氢酶（复合物I）和琥珀酸脱氢酶（复合物II）的活性受到抑制，伴随着gas-1、nuo-1和mev-1的表达减少。gas-1和mev-1的RNAi增强线粒体功能障碍并降低6-PPDQ暴露线虫的寿命。GAS-1和MEV-1并行起调节6-PPDQ毒性以减少寿命的作用。胰岛素肽和胰岛素信号通路在GAS-1和MEV-1的下游作用以控制6-PPDQ对寿命的毒性。此外，daf-16的靶向基因sod-2和sod-3的RNAi在减少寿命和引起活性氧（ROS）产生方面引起对6-PPDQ毒性的敏感性。因此,环境相关浓度（ERC）的6-PPDQ可能通过影响线粒体复合物I和II引起线粒体功能障碍，通过影响生物体中的胰岛素信号与寿命减少有关。
