The ROS–FOXO pathway mediates broad-spectrum detoxification of acaricides in Tetranychus cinnabarinus

Abstract Arthropods have evolved advanced metabolic detoxification pathways that have helped them adapt to complex stresses induced by plant secondary metabolites and synthetic pesticides. Nonetheless, how xenobiotics induce the suite of intracellular metabolic changes important for detoxification i...

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Bibliographic Details
Main Authors: Xiang Wen, Kaiyang Feng, Peng Wei, Jinhang Li, Ming Li, Wei Dou, Zhaojiang Guo, Youjun Zhang, Lin He
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-025-08726-0
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Summary:Abstract Arthropods have evolved advanced metabolic detoxification pathways that have helped them adapt to complex stresses induced by plant secondary metabolites and synthetic pesticides. Nonetheless, how xenobiotics induce the suite of intracellular metabolic changes important for detoxification in arthropods remains unexplored. In this study, we found that the ancient oxidative stress signaling pathway has adapted to transmit the detoxification signal in T. cinnabarinus, where accumulation of reactive oxygen species (ROS) plays a crucial role in initiating detoxification metabolism. Acaricides exposure led to ROS accumulation, resulting in the activation of Forkhead box O (FOXO) that in turn upregulates the expression of downstream xenobiotic sensors, including CncC, AhR, and HR96. These xenobiotic sensors then upregulate the expression of downstream detoxification genes, helping mites metabolically detoxify acaricides. This study reveals a cascade-amplifying mechanism for broad-spectrum detoxification in T. cinnabarinus that is initiated through ROS–FOXO triggering broad-spectrum detoxification of xenobiotics. These findings further elucidate the adaptive evolution of arthropods and suggest new avenues for novel pesticides and pest control.
ISSN:2399-3642