6-PPD quinone causes alteration in ubiquinone-mediated complex III associated with toxicity on mitochondrial function and longevity in Caenorhabditis elegans

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. • Alteration of mitochondrial complex I/II induced by 6-PPDQ inhibited the complex III activity. • CLK-1 and ISP-1 were involved in the control of 6-PPDQ toxicity on mitochondrial dysfunction. • GAS-1 and MEV-1 acted upstreams of CLK-1/ISP-1 in regulating6-PPDQ toxicity on lifespan. • Changes of mitochondrial complexes inhibited the mt UPR to induce 6-PPDQ toxicity.