2. Academic Validation
  3. Neuronal PRDX-2-Mediated ROS Signaling Regulates Food Digestion via peripheral UPRmt Activation

Neuronal PRDX-2-Mediated ROS Signaling Regulates Food Digestion via peripheral UPRmt Activation

  • Nat Commun. 2024 Dec 4;15(1):10582. doi: 10.1038/s41467-024-55013-3.
Yating Liu # 1,  Qian Li # 1,  Guojing Tian 1,  Xinyi Zhou 1,  Panpan Chen 1,  Bo Chen 1,  Zhao Shan 2,  Bin Qi 3
Affiliations

Affiliations

  • 1 Southwest United Graduate School, Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory of Conservation and Utilization of Bio-resources in Yunnan Center for Life Sciences, School of Life Sciences, Yunnan University, Kunming, China.
  • 2 Southwest United Graduate School, Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory of Conservation and Utilization of Bio-resources in Yunnan Center for Life Sciences, School of Life Sciences, Yunnan University, Kunming, China. shanzhaolab@163.com.
  • 3 Southwest United Graduate School, Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory of Conservation and Utilization of Bio-resources in Yunnan Center for Life Sciences, School of Life Sciences, Yunnan University, Kunming, China. qb@ynu.edu.cn.
  • # Contributed equally.
PMID: 39632952 DOI: 10.1038/s41467-024-55013-3
Abstract

All organisms depend on food digestion for survival, yet the brain-gut signaling mechanisms that regulate this process are not fully understood. Here, using an established C. elegans digestion model, we uncover a pathway in which neuronal ROS (free radicals) signal the intestine to suppress digestion. Genetic screening reveals that reducing genes responsible for maintaining ROS balance increases free radicals and decreases digestion. PRDX-2 knockout in olfactory neurons (AWC) elevates ROS and reduces digestive capacity, mediated by the neuropeptide NLP-1 and activation of the mitochondrial unfolded protein response (UPRmt) in the intestine. Additionally, over-expressing nlp-1 or ablating AWC neurons both trigger UPRmt and inhibit digestion. These findings reveal a brain-gut connection in which neuronal PRDX-2-mediated ROS signaling modulates food digestion, highlighting a critical role of free radicals in shutting down digestion to alleviate stress and reduce food consumption.

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