ArticleOncotarget2016
Crosstalk between Ca2+ signaling and mitochondrial H2O2 is required for rotenone inhibition of mTOR signaling pathway leading to neuronal apoptosis.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Systematic Review of Calcium Channels and Intracellular Calcium Signaling: Relevance to Pesticide Neurotoxicity.International journal of molecular sciences · 2021Pooled it
- Nicotinamide counteracts Rotenone-induced mitochondrial and neuronal dysfunction in a translational early-life model.Scientific reports · 2026Article
- SenolyticSynergy: An Attention-Based Network for Discovering Novel Senolytic Combinations via Human Aging Genomics.International journal of molecular sciences · 2025Article
- Autophagy is involved in the toxicity of the biocontrol agent GC16 against Tetranychus pueraricola (Acari: Tetranychidae) based on transcriptomic and proteomic analyses.BMC genomics · 2025Article
- Article
- Implications of reactive oxygen species in lung cancer and exploiting it for therapeutic interventions.Medical oncology (Northwood, London, England) · 2022Review
- Impact of Environmental Risk Factors on Mitochondrial Dysfunction, Neuroinflammation, Protein Misfolding, and Oxidative Stress in the Etiopathogenesis of Parkinson's Disease.International journal of molecular sciences · 2022Review
- Lysosomal CaNature communications · 2022Article
- A mitochondria cluster at the proximal axon initial segment controls axodendritic TAU trafficking in rodent primary and human iPSC-derived neurons.Cellular and molecular life sciences : CMLS · 2022Article
- Mitochondrial retrograde signalling in neurological disease.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2020Article
- Aquaporin-3 deficiency slows cyst enlargement in experimental mouse models of autosomal dominant polycystic kidney disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Integration of CaOncogene · 2018Article
- Chromaffin cells as a model to evaluate mechanisms of cell death and neuroprotective compounds.Pflugers Archiv : European journal of physiology · 2018Review
- Sarm1 induction and accompanying inflammatory response mediates age-dependent susceptibility to rotenone-induced neurotoxicity.Cell death discovery · 2018Article
- Melatonin Mitigates Kainic Acid-Induced Neuronal Tau Hyperphosphorylation and Memory Deficits through Alleviating ER Stress.Frontiers in molecular neuroscience · 2018Article
- CaMKII is involved in subcellular CaOncotarget · 2017Article
- Transcriptome Analyses Shed New Insights into Primary Metabolism and Regulation ofFrontiers in plant science · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Rotenone, a neurotoxic pesticide, induces loss of dopaminergic neurons related to Parkinson's disease. Previous studies have shown that rotenone induces neuronal apoptosis partly by triggering hydrogen peroxide (H2O2)-dependent suppression of mTOR pathway. However, the underlying mechanism is not fully understood. Here, we show that rotenone elevates intracellular free calcium ion ([Ca2+]i) level, and activates CaMKII, resulting in inhibition of mTOR signaling and induction of neuronal apoptosis. Chelating [Ca2+]i with BAPTA/AM, preventing extracellular Ca2+ influx using EGTA, inhibiting CaMKII with KN93, or silencing CaMKII significantly attenuated rotenone-induced H2O2 production, mTOR inhibition, and cell death. Interestingly, using TTFA, antimycin A, catalase or Mito-TEMPO, we found that rotenone-induced mitochondrial H2O2 also in turn elevated [Ca2+]i level, thereby stimulating CaMKII, leading to inhibition of mTOR pathway and induction of neuronal apoptosis. Expression of wild type mTOR or constitutively active S6K1, or silencing 4E-BP1 strengthened the inhibitory effects of catalase, Mito-TEMPO, BAPTA/AM or EGTA on rotenone-induced [Ca2+]i elevation, CaMKII phosphorylation and neuronal apoptosis. Together, the results indicate that the crosstalk between Ca2+ signaling and mitochondrial H2O2 is required for rotenone inhibition of mTOR-mediated S6K1 and 4E-BP1 pathways. Our findings suggest that how to control over-elevation of intracellular Ca2+ and overproduction of mitochondrial H2O2 may be a new approach to deal with the neurotoxicity of rotenone.
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Registered trials
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