Edited by Paul Garrity, Brandeis University, and accepted by Editorial Board Member Michael Rosbash May 2, 2019 (received for review April 9, 2019)
Light-absorbing pigments undergo chemical changes via excitation of electrons. The electron excitation may generate reactive chemicals such as free radicals, and eventually reactive oxygen species, causing tissue damage like sunburn. Such pigments able to exert toxic effects on light illumination are regarded as phototoxins. Despite advances of our chemical knowledge on phototoxicity, the prediction of intrinsic pigment phototoxicity has been limited. Our study shows that the insect chemical receptor called Transient Receptor Potential Ankyrin 1 (TRPA1) is able to discern intrinsic phototoxins among pigments, for which TRPA1 needs the capability of sensing nucleophiles, chemical compounds with strong electron-donating tendency. Accordingly, understanding insect chemical receptor TRPA1 leads to the discovery of nucleophilicity as a chemical signature of intrinsic phototoxicity.
Pigments often inflict tissue-damaging and proaging toxicity on light illumination by generating free radicals and reactive oxygen species (ROS). However, the molecular mechanism by which organisms sense phototoxic pigments is unknown. Here, we discover that Transient Receptor Potential Ankyrin 1-A isoform [TRPA1(A)], previously shown to serve as a receptor for free radicals and ROS induced by photochemical reactions, enables Drosophila melanogaster to aphotically sense phototoxic pigments for feeding deterrence. Thus, TRPA1(A) detects both cause (phototoxins) and effect (free radicals and ROS) of photochemical reactions. A group of pigment molecules not only activates TRPA1(A) in darkness but also generates free radicals on light illumination. Such aphotic detection of phototoxins harboring the type 1 (radical-generating) photochemical potential requires the nucleophile-sensing ability of TRPA1. In addition, agTRPA1(A) from malaria-transmitting mosquitoes Anopheles gambiae heterologously produces larger current responses to phototoxins than Drosophila TRPA1(A), similar to their disparate nucleophile responsiveness. Along with TRPA1(A)-stimulating capabilities, type 1 phototoxins exhibit relatively strong photo-absorbance and low energy gaps between the highest occupied molecular orbital and the lowest unoccupied molecular orbital. However, TRPA1(A) activation is more highly concordant to type 1 phototoxicity than are those photochemical parameters. Collectively, nucleophile sensitivity of TRPA1(A) allows flies to taste potential phototoxins for feeding deterrence, preventing postingestive photo-injury. Conversely, pigments need to bear high nucleophilicity (electron-donating propensity) to act as type 1 phototoxins, which is consistent with the fact that transferring photoexcited electrons from phototoxins to other molecules causes free radicals. Thus, identification of a sensory mechanism in Drosophila reveals a property fundamental to type 1 phototoxins.
Author contributions: E.J.D., T.J.A., S.-T.K., and K.K. designed research; E.J.D., T.J.A., H.S., H.J., and S.-T.K. performed research; E.J.D., T.J.A., H.S., H.J., H.-W.K., and K.K. analyzed data; and H.-W.K. and K.K. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission. P.G. is a guest editor invited by the Editorial Board.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1905998116/-/DCSupplemental.
Published under the PNAS license.
