Expression Data of Reactive Oxygen Species Signalling in C. elegans
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ABSTRACT:
ORGANISM(S): Caenorhabditis elegans
PROVIDER: GSE54024 | GEO | 2014/05/08
SECONDARY ACCESSION(S): PRJNA234376
REPOSITORIES: GEO
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Project description:We have shown that worms that possess mutations in two electron transport chain subunits live longer due to mtROS signalling. Wild type worms can also live longer by treatment with the pro-oxidant paraquat. Paraquat treatment is not additive to the mutations in the ETC subunits. We aimed to determine the underlying changes in gene expression that were common to both paraquat treatment and the two mutations. We also have shown genetically that the mtROS signal that leads to extended lifespan is dependent on CED-4. We generated double mutants that lack functional CED-4 with the two mutations in the ETC subunits. We have found that a large number of gene expression changes by mtROS signalling are reverted by loss of CED-4. Young adult C. elegans were grown using a 4-hour synchronized lay and harvested by hand picking. At least three biological repeats were obtained for each condition. Worm RNA was extracted and prepared for hybridization to Affymetrix chips. We compared the gene expression patterns of genetic mutants and the wild type treated with paraquat all against a wild type control. We sought to obtain a common pattern of expression between two genetic mutants, isp-1 and nuo-6, and paraquat treatment.
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Project description:The goal of this analysis was to profile the gene expression signatures associated to different neuronal doses of IF1. The mitochondrial ATP synthase produces ATP by oxidative phosphorylation and integrates different signals to regulate cellular functions and fate. The ATPase inhibitory factor 1 (IF1) is a structurally-disordered protein that inhibits the ATP synthase, contributing to metabolic reprogramming and signalling through mitochondrial reactive oxygen species (mtROS). mtROS regulate kinases and transcription factors in mitohormetic responses that favour adaptation to toxic insults. IF1 is tissue-specifically expressed and in human and mouse brain is in molar excess over the ATP synthase. Herein, we have used genetic approaches to ablate or overexpress IF1 in neurons to investigate its role in brain functions. IF1 inhibits a fraction of the ATP synthase under physiological conditions and regulates respiration, mtROS production and mitochondrial structure. Transcriptomic, proteomic and metabolomic analyses indicate that IF1 regulates synaptic transmission and cognition. Ablation of IF1 impairs short-term memory whereas IF1 overexpression increases basal synaptic transmission and learning by mtROS-dependent activation of the extracellular signal-regulated kinases 1/2 (ERK 1/2). Overall, we show that IF1 dose plays a fundamental role in the regulation of neuronal function by controlling the fraction of inhibited ATP synthase that acts as source of mitohormetic mtROS, further emphasizing the ATP synthase/IF1 as promising targets to treat cognitive disorders.
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