6-PPD quinone causes alteration in ubiquinone-mediated complex III associated with toxicity on mitochondrial function and longevity in Caenorhabditis elegans
Xin Hua, Dayong Wang
Abstract
Ubiquinone (coenzyme Q)-mediated complex III acts as the important hub in electron transport chain . In Caenorhabditis elegans , we aimed to examine the effect of 6-PPD quinone (6-PPDQ) on ubiquinone-mediated complex III and its association with 6-PPDQ toxicity induction. In nematodes, 6-PPDQ (1–10 μg/L) decreased complex III activity. Meanwhile, expression of clk-1 governing coenzyme Q synthesis was increased by 6-PPDQ (1–10 μg/L), and RNA interference (RNAi) of clk-1 suppressed 6-PPDQ toxicity on mitochondrial function and longevity. Exposure to 6-PPDQ further increased expression of isp-1 encoding component of complex III, and isp-1 RNAi caused resistance to 6-PPDQ toxicity on mitochondrial function and longevity. Mitochondrial unfolded protein response (mt UPR) could be increased by clk-1 and isp-1 RNAi after 6-PPDQ exposure, which was associated with altered lonp-1 and haf-1 expressions. The 6-PPDQ-caused mitochondrial dysfunction could be accelerated by haf-1 RNAi and inhibited by lonp-1 RNAi. Therefore, alteration in ubiquinone-mediated complex III was related to 6-PPDQ-induced toxicity on mitochondrial function and longevity by affecting mitochondrial UPR activation.