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

Yating Liu, Qian Li, Guojing Tian, Xinyi Zhou, Panpan Chen, Bo Chen, Zhao Shan () and Bin Qi ()
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Yating Liu: Yunnan University
Qian Li: Yunnan University
Guojing Tian: Yunnan University
Xinyi Zhou: Yunnan University
Panpan Chen: Yunnan University
Bo Chen: Yunnan University
Zhao Shan: Yunnan University
Bin Qi: Yunnan University

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-55013-3

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