2. Academic Validation
  3. A Cold Stress-Activated Endocrine Sentinel Chemical Hormone Promotes Insect Survival via Mitochondrial Adaptations Through the Adipokinetic Hormone Receptor

A Cold Stress-Activated Endocrine Sentinel Chemical Hormone Promotes Insect Survival via Mitochondrial Adaptations Through the Adipokinetic Hormone Receptor

  • Adv Sci (Weinh). 2026 Feb;13(10):e09822. doi: 10.1002/advs.202509822.
Jiao Zhou 1,  Junxian Chen 1 2,  Hongxia Zhang 1,  Lu Guo 3,  Kevin Mai 4,  Elijah Abraham 4,  Dilip V Prajapati 4,  Yue Chang 1 2,  Jing Ning 1,  Xinchen Wang 1 2,  Defeng Li 3,  Dan-Dan Zhang 5,  Jianghua Sun 6,  Rebecca A Butcher 4,  Lilin Zhao 1 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
  • 2 CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, Beijing, China.
  • 3 State Key Laboratory of Microbial Diversity and Innovative Utilization, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
  • 4 Department of Chemistry, University of Florida, Gainesville, Florida, USA.
  • 5 Department of Biology, Lund University, Lund, Sweden.
  • 6 College of Life Science, Institute of Life Science and Green Development, Hebei University, Hebei, China.
  • 7 Shanxi Fen River Plain Farmland Shelterbelt Ecosystem National Observation Research Station, Jinzhong, China.
PMID: 41431176 DOI: 10.1002/advs.202509822
Abstract

Seasonal temperature fluctuations present a major survival challenge for insects, requiring physiological adaptation that confers resilience to cold stress. However, the hormone mechanisms governing mitochondrial adaptation to overcome cold stress remain poorly understood. Here, we identify that the endogenous ascaroside C9 (asc-C9) acts as a chemical signal that markedly improves survival following acute cold exposure by coupling lipolysis to mitochondrial adaptation. We show that diapause larvae maintain compact mitochondrial cristae and display 2.7-fold higher post-chill survival compare to non-diapause larvae, whose mitochondria undergo swelling and fragmentation. Cold stress triggers diapause-specific accumulation of asc-C9 (ascr#10) in the subcutaneous fat body. Exogenous asc-C9 recruits the adipokinetic hormone receptor (AKHR) to activate the Peroxisome Proliferator-activated Receptor gamma coactivator 1-alpha (PGC1α)-uncoupling protein 4 (UCP4) axis, thereby stimulating mitochondrial biogenesis, enhance uncoupled respiration, lowering the adenosine triphosphate/adenosine diphosphate (ATP/ADP) ratio, and synchronously accelerate lipid mobilization and increasing cold resilience. This asc-C9-AKHR-mitochondria module is functionally conserved in Drosophila melanogaster and Caenorhabditis elegans, indicating that ascaroside-mediated metabolic reprogramming is an ancient stress-adaptation strategy. Our findings reveal a sentinel hormone-driven lipid-to-mitochondria circuit that enables insects to survive extreme cold through targeted mitochondrial flexibility.

Keywords

adipokinetic hormone receptor; ascarosides hormone; diapause; mitochondrial biogenesis; mitochondrial uncoupling; survival.

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