Exposure to 6-PPD quinone inhibits ATP synthesis by causing damage on mitochondrial complex V in Caenorhabditis elegans

ATP synthesis plays a pivotal role in maintaining physiological state of organisms, which is controlled by mitochondrial complex V. In Caenorhabditis elegans , we found that 6-PPD quinone (6-PPDQ) inhibited complex V activity. Expressions of atp-2 , F58F12.1 , asb-1 , and Y82E9BR.3 encoding V-F 1 and V-F 0 subunits were also increased by 6-PPDQ, and RNAi of these genes increased ATP content after 6-PPDQ exposure. Meanwhile, 6-PPDQ-induced mitochondrial UPR was enhanced by atp-2 , F58F12.1 , asb-1 , and Y82E9BR.3 RNAi, and expression of these 4 genes and complex V activity were influenced by RNAi of genes encoding components of complex I-IV. atp-2 , F58F12.1 , asb-1 , and Y82E9BR.3 functioned in intestine, neurons, and germline to control the 6-PPDQ caused decrease in ATP content and induction of mitochondrial UPR. Moreover, RNAi of atp-2 , F58F12.1 , asb-1 , and Y82E9BR.3 increased expressions of genes governing citric acid cycle and elevated NADH and FADH 2 contents in 6-PPDQ exposed nematodes. 6-PPDQ has potential to bind to ATP-2, F58F12.1, ASB-1, and Y82E9BR.3. Therefore, potential direct effect of 6-PPDQ exposure in disrupting complex V was suggested to decrease the ATP content in organisms.