scholarly journals Mitochondrial hydrogen peroxide positively regulates neuropeptide secretion during diet-induced activation of the oxidative stress response

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Qi Jia ◽  
Derek Sieburth

AbstractMitochondria 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 (mtH2O2) 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 mtH2O2 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. mtH2O2-induced FLP-1 secretion activates the oxidative stress response transcription factor SKN-1/Nrf2 in distal tissues and protects animals from ROS-mediated toxicity. mtH2O2 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 mtH2O2 in linking diet-induced changes in mitochondrial homeostasis with neuropeptide secretion.

2018 ◽  
Vol 165 (2) ◽  
pp. 197-204 ◽  
Author(s):  
Eun-Ji Hong ◽  
Haeri Jeong ◽  
Dong-Seok Lee ◽  
Younhee Kim ◽  
Heung-Shick Lee

2009 ◽  
Vol 47 (8) ◽  
pp. 814-823 ◽  
Author(s):  
Weifa Zheng ◽  
Yanxia Zhao ◽  
Meimei Zhang ◽  
Zhiwen Wei ◽  
Kangjie Miao ◽  
...  

Exposome ◽  
2021 ◽  
Author(s):  
Karthik Suresh Arulalan ◽  
Javier Huayta ◽  
Jonathan W Stallrich ◽  
Adriana San-Miguel

Abstract Chemical agents released into the environment can induce oxidative stress in organisms, which is detrimental for health. Although environmental exposures typically include multiple chemicals, organismal studies on oxidative stress derived from chemical agents commonly study exposures to individual compounds. In this work, we explore how chemical mixtures drive the oxidative stress response under various conditions in the nematode C. elegans, by quantitatively assessing levels of gst-4 expression. Our results indicate that naphthoquinone mixtures drive responses differently than individual components, and that altering environmental conditions, such as increased heat and reduced food availability, result in dramatically different oxidative stress responses mounted by C. elegans. When exposed to heat, the oxidative stress response is diminished. Notably, when exposed to limited food, the oxidative stress response specific to juglone is significantly heightened, while identified antagonistic interactions between some naphthoquinone components in mixtures are abolished. This implies that organismal responses to xenobiotics is confounded by environment and stressor interactions. Given the high number of variables under study, and their potential combinations, a simplex centroid design was used to capture such non-trivial response over the design space. This makes the case for the adoption of Design of Experiments approaches as they can greatly expand the experimental space probed in noisy biological readouts, and in combinatorial experiments. Our results also reveal gaps in our current knowledge of the organismal oxidative stress response, which can be addressed by employing sophisticated design of experiments approaches to identify significant interactions.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 684-684
Author(s):  
Raul Castro-Portuguez ◽  
Jeremy Meyers ◽  
Sam Freitas ◽  
Hope Dang ◽  
Emily Turner ◽  
...  

Abstract Aging is characterized by a progressive decline in the normal physiological functions of an organism, ultimately leading to mortality. Metabolic changes throughout the aging process disrupt the balance and homeostasis of the cell. The kynurenine metabolic pathway is the sole de novo biosynthetic pathway for producing NAD+ from ingested tryptophan. Altered kynurenine pathway activity is associated with both aging and a variety of age-associated diseases, and kynurenine-based interventions can extend lifespan in Caenorhabditis elegans. Our laboratory recently demonstrated knockdown of the kynurenine pathway enzymes kynureninase (KYNU) or 3-hydroxyanthranilic acid dioxygenase (HAAO) increases lifespan by 20-30% in C elegans. However, the mechanism of how these interventions may modulate response against different stressors during the aging process has yet to be explored. Fluorescent reporter strains show the stress-responsive transcription factors skn-1 (ortholog of NRF2/NFE2L2; oxidative stress response) and hif-1 (ortholog of HIF1A; hypoxic stress response) to be highly upregulated when the kynurenine pathway is inhibited. We also demonstrated the increase expression of gst-4 and gcs-1 (transcriptional targets skn-1), which are involved in production of the antioxidant glutathione (GSH), as well as upregulation of cysl-2 (transcriptional target of hif-1), a regulator of cysteine biosynthesis from serine. We hypothesize that lifespan extension resulting from kynurenine pathway inhibition is mediated, at least in part, by upregulation of these transcription factors, providing elevated defense against oxidative stress and hypoxic stress.


2009 ◽  
pp. 1-10 ◽  
Author(s):  
Weifa Zheng ◽  
Yanxia Zhao ◽  
Meimei Zhang ◽  
Zhiwen Wei ◽  
Kangjie Miao ◽  
...  

2011 ◽  
Vol 77 (18) ◽  
pp. 6426-6432 ◽  
Author(s):  
Zomary Flores-Cruz ◽  
Caitilyn Allen

ABSTRACTThe plant pathogenRalstonia solanacearum, which causes bacterial wilt disease, is exposed to reactive oxygen species (ROS) during tomato infection and expresses diverse oxidative stress response (OSR) genes during midstage disease on tomato. TheR. solanacearumgenome predicts that the bacterium produces multiple and redundant ROS-scavenging enzymes but only one known oxidative stress response regulator, OxyR. AnR. solanacearumoxyRmutant had no detectable catalase activity, did not grow in the presence of 250 μM hydrogen peroxide, and grew poorly in the oxidative environment of solid rich media. This phenotype was rescued by the addition of exogenous catalase, suggesting thatoxyRis essential for the hydrogen peroxide stress response. Unexpectedly, theoxyRmutant strain grew better than the wild type in the presence of the superoxide generator paraquat. Gene expression studies indicated thatkatE,kaG,ahpC1,grxC, andoxyRitself were each differentially expressed in theoxyRmutant background and in response to hydrogen peroxide, suggesting thatoxyRis necessary for hydrogen peroxide-inducible gene expression. Additional OSR genes were differentially regulated in response to hydrogen peroxide alone. The virulence of theoxyRmutant strain was significantly reduced in both tomato and tobacco host plants, demonstrating thatR. solanacearumis exposed to inhibitory concentrations of ROSin plantaand that OxyR-mediated responses to ROS during plant pathogenesis are important forR. solanacearumhost adaptation and virulence.


2005 ◽  
Vol 109 (2) ◽  
pp. 150-158 ◽  
Author(s):  
Maria B. Angelova ◽  
Svetlana B. Pashova ◽  
Boryana K. Spasova ◽  
Spassen V. Vassilev ◽  
Lyudmila S. Slokoska

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