Mitochondrial Hydrogen Peroxide Positively Regulates Neuropeptide Secretion During Diet-induced Activation of the Oxidative Stress Response

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Apr 17

PMID 33863916

Citations 26

Authors

Qi Jia

Derek Sieburth

Affiliations

Soon will be listed here.

Abstract

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 (mtHO) 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 mtHO 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. mtHO-induced FLP-1 secretion activates the oxidative stress response transcription factor SKN-1/Nrf2 in distal tissues and protects animals from ROS-mediated toxicity. mtHO 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 mtHO in linking diet-induced changes in mitochondrial homeostasis with neuropeptide secretion.

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