The pleiotropic AMPK–CncC signaling pathway regulates the trade-off between detoxification and reproduction

Heng Jiang, Xiangkun Meng, Nan Zhang, Huichen Ge, Jiaping Wei, Kun Qian, Yang Zheng, Yoonseong Park, Subba Reddy Palli, Jianjun Wang

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


The association of decreased fecundity with insecticide resistance and the negative sublethal effects of insecticides on insect reproduction indicates the typical trade-off between two highly energy-demanding processes, detoxification and reproduction. However, the underlying mechanisms are poorly understood. The energy sensor adenosine monophosphate-activated protein kinase (AMPK) and the transcription factor Cap “n” collar isoform C (CncC) are important regulators of energy metabolism and xenobiotic response, respectively. In this study, using the beetle Tribolium castaneum as a model organism, we found that deltamethrin-induced oxidative stress activated AMPK, which promoted the nuclear translocation of CncC through its phosphorylation. The CncC not only acts as a transcription activator of cytochrome P450 genes but also regulates the expression of genes coding for ecdysteroid biosynthesis and juvenile hormone (JH) degradation enzymes, resulting in increased ecdysteroid levels as well as decreased JH titer and vitellogenin (Vg) gene expression. These data show that in response to xenobiotic stress, the pleiotropic AMPK–CncC signaling pathway mediates the trade-off between detoxification and reproduction by up-regulating detoxification genes and disturbing hormonal homeostasis.

Original languageEnglish
Article numbere2214038120
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number10
StatePublished - Mar 7 2023

Bibliographical note

Publisher Copyright:
Copyright © 2023 the Author(s). Published by PNAS.


  • AMPK
  • CncC
  • detoxification
  • reproduction
  • xenobiotic stress

ASJC Scopus subject areas

  • General


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