Exposure to 6-PPD quinone causes damage on mitochondrial complex I/II associated with lifespan reduction in Caenorhabditis elegans

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 0.1-10μg/L was performed form L1 larvae to adult day-1. Exposure to 6-PPDQ (1 and 10μg/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. Environmental implication The 6-PPD quinone (6-PPDQ) has been widely distributed in the environment and showed bioavailability to environmental organisms. In Caenorhabditis elegans, 6-PPDQ at environmentally relevant concentrations (ERCs) could result in mitochondrial dysfunction, which was associated with altered activities and expressions of genes encoding components in complex I and II. Moreover, components on complex I and II regulated 6-PPDQ toxicity in reducing lifespan by inhibiting insulin peptides and receptor DAF-2. Our results suggested possibility of 6-PPDQ at ERCs in causing damage on mitochondrial complexes and in reducing lifespan in organisms.