Uncovering Hidden Bioenergetic Effects of DEET: Is Mitochondrial Complex I a Primary Target?

Uncovering Hidden Bioenergetic Effects of DEET: Is Mitochondrial Complex I a Primary Target?

Alvin Sherman Library

DEET (N, N-diethyl-m-toluamide) is one of the most common insect repellents worldwide and is generally regarded as safe for humans. As such, DEET is available as a nonprescribed product to the public for topical application, with concentrations reaching up to 4.0M. However, new studies in other organisms suggest it may have a greater physiological effect than thought before. Research has shown that DEET can reduce Photosystem II activity in algae, alter red blood cell production and lipid metabolism in fish, and cause developmental and cardiovascular issues in zebrafish embryos. These findings point toward disruptions in mitochondrial and oxidative processes. Mammalian studies show similar trends, including increased cytochrome c release and changes in the activity of key metabolic enzymes, suggesting that DEET may influence additional biochemical processes. Interestingly, little is known about how DEET affects the mitochondrial electron transport system (ETS). To address this gap, we tested how different concentrations of DEET impact the activity of ETS enzymes, and the coupling of electron transport to ATP production. Preliminary findings on isolated mitochondria show complete inhibition of NADH oxidoreductase (Complex I of the ETS) activity of the ETS at a concentration of 6.0 mM DEET. Assays on succinate dehydrogenase (Complex II of the ETS) activity show a marginal reduction respiration after addition of 6 mM DEET, but this may be attributed to a slight reduction in electron backflow through complex I in the preliminary trials. Further are ongoing to disentangle the complex-specific effects of DEET on mitochondrial function.