期刊
NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -出版社
NATURE RESEARCH
DOI: 10.1038/s41467-021-22561-x
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资金
- NIH National Center for Research Resources (NCRR)
- Southern California Environmental Health Sciences Center [P30ES007048]
- National Institutes of Health (NIH) [NS099414]
Mitochondria play a crucial role in connecting metabolism with neurotransmitter release. The study demonstrates that endogenous hydrogen peroxide produced by axonal mitochondria acts as a signaling molecule to selectively regulate neuropeptide secretion in C. elegans.
Mitochondria play a pivotal role in the generation of signals coupling metabolism with neurotransmitter release, but a role for mitochondrial-produced ROS in regulating neurosecretion has not been described. Here we show that endogenously produced hydrogen peroxide originating from axonal mitochondria (mtH(2)O(2)) functions as a signaling cue to selectively regulate the secretion of a FMRFamide-related neuropeptide (FLP-1) from a pair of interneurons (AIY) in C. elegans. We show that pharmacological or genetic manipulations that increase mtH(2)O(2) levels lead to increased FLP-1 secretion that is dependent upon ROS dismutation, mitochondrial calcium influx, and cysteine sulfenylation of the calcium-independent PKC family member PKC-1. mtH(2)O(2)-induced FLP-1 secretion activates the oxidative stress response transcription factor SKN-1/Nrf2 in distal tissues and protects animals from ROS-mediated toxicity. mtH(2)O(2) levels in AIY neurons, FLP-1 secretion and SKN-1 activity are rapidly and reversibly regulated by exposing animals to different bacterial food sources. These results reveal a previously unreported role for mtH(2)O(2) in linking diet-induced changes in mitochondrial homeostasis with neuropeptide secretion. Mitochondria play a pivotal role in the generation of signals coupling metabolism with neurotransmitter release, though underlying mechanisms remain unknown. Here the authors show that endogenously produced hydrogen peroxide originating from axonal mitochondria functions as a signaling cue to selectively regulate neuropeptide secretion in C. elegans.
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