Proteomic analysis reveals oxidative stress-induced activation of Hippo signaling in thiamethoxam-exposed Drosophila

Thiamethoxam (THIA) is a widely used neonicotinoid insecticide. However, the toxicity and defense mechanisms activated in THIA-exposed insects are unclear. Here, we used isobaric tags for relative and absolute quantitation (iTRAQ) proteomics technology to identify changes in protein expression in THIA-exposed Drosophila. We found that the antioxidant proteins Cyp6a23 and Dys were upregulated, whereas vir-1 was downregulated, which may have been detoxification in response to THIA exposure. Prx5 downregulation promoted the generation of reactive oxygen species. Furthermore, the accumulation of reactive oxygen species led to the induction of antioxidant defenses in THIA-exposed Drosophila, thereby enhancing the levels of oxidative stress markers (e.g., superoxide dismutase, glutathione S-transferase, and glutathione) and reducing catalase expression. Furthermore, the Hippo signaling transcription coactivator Yki was inactivated by THIA. Our results suggesting that Hippo signaling may be necessary to promote insect survival in response to neonicotinoid insecticide toxicity. •One hundred and seventy-one differentially expressed proteins were identified.•Thiamethoxam induced excessive accumulation of reactive oxygen species.•Antioxidant defenses were activated in response to THIA exposure.•Hippo signaling was activated by THIA exposure.