Keeping Wavering Bonds: Deactivation-Induced Signaling by Reactive Electrophiles

, using a customized tissue-specific screen for HNE-sensor proteins. Consistent with the concepts of active site partitioning, HNE also emerged as a substrate of Cyp-33e1. We next discovered that HNE changed lipid storage in worms in a Cyp-33e1-dependent manner. We proposed that the product of Cyp-33e1 detoxifying HNE was responsible for this change in lipid storage and were able to show that 4-hydroxynonenoic acid (HNA), the product of Cyp-33e1 oxidation of HNE, causes this phenotype. We have dubbed this new signaling mode, "deactivation signaling". It sets an important precedent for how the bioactivity of HNE is considered, and we discuss the ramifications of this result in this perspective.