ArticleToxicology2021
Multiple metabolic changes mediate the response of Caenorhabditis elegans to the complex I inhibitor rotenone.
Article in Toxicology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 42 citations in OpenAlex.
- Article
- Progeny effects of rotenone exposure depend on parental toxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- The succinate prodrug NV354 prevents brain lesions and late-stage motor dysfunction in mitochondrial complex I deficiency.iScience · 2026Article
- Article
- Gastrodin inhibits hexokinase-2 mediated glycolysis to rescue rotenone-damaged PC12 cells.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Oenological tannins mitigate rotenone-induced mitochondrial impairments and oxidative stress, with concomitant detection of urolithin A in the brain.Biochemistry and biophysics reports · 2025Article
- Inhibition of Mitochondrial Complex III Causes Dopaminergic Neurodegeneration by Redox Stress inbioRxiv : the preprint server for biology · 2025Article
- Rotenone adaptation promotes migration and invasion of p53-wild-type colon cancer through lipid metabolism.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- Rescue of a Rotenone Model of Parkinson's Disease inInternational journal of molecular sciences · 2025Article
- VDR and deubiquitination control neuronal oxidative stress and microglial inflammation in Parkinson's disease.Cell death discovery · 2024Article
- Developmental regulation of cellular metabolism is required for intestinal elongation and rotation.Development (Cambridge, England) · 2024Article
- Article
- Chronic high-sugar diet in adulthood protects Caenorhabditis elegans from 6-OHDA-induced dopaminergic neurodegeneration.BMC biology · 2023Article
- Mitochondria in the Spotlight:Cells · 2023Review
- Does treatment with autophagy-enhancers and/or ROS-scavengers alleviate behavioral and neurochemical consequences of low-dose rotenone-induced mild mitochondrial dysfunction in mice?Molecular psychiatry · 2023Article
- SERCA inhibition improves lifespan and healthspan in a chemical model of Parkinson disease inFrontiers in pharmacology · 2023Article
- Organismal and Cellular Stress Responses upon Disruption of Mitochondrial Lonp1 Protease.Cells · 2022Article
- Article
- Rotenone ModulatesFrontiers in immunology · 2022Article
- Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Rotenone, a mitochondrial complex I inhibitor, has been widely used to study the effects of mitochondrial dysfunction on dopaminergic neurons in the context of Parkinson's disease. Although the deleterious effects of rotenone are well documented, we found that young adult Caenorhabditis elegans showed resistance to 24 and 48 h rotenone exposures. To better understand the response to rotenone in C. elegans, we evaluated mitochondrial bioenergetic parameters after 24 and 48 h exposures to 1 μM or 5 μM rotenone. Results suggested upregulation of mitochondrial complexes II and V following rotenone exposure, without major changes in oxygen consumption or steady-state ATP levels after rotenone treatment at the tested concentrations. We found evidence that the glyoxylate pathway (an alternate pathway not present in higher metazoans) was induced by rotenone exposure; gene expression measurements showed increases in mRNA levels for two complex II subunits and for isocitrate lyase, the key glyoxylate pathway enzyme. Targeted metabolomics analyses showed alterations in the levels of organic acids, amino acids, and acylcarnitines, consistent with the metabolic restructuring of cellular bioenergetic pathways including activation of complex II, the glyoxylate pathway, glycolysis, and fatty acid oxidation. This expanded understanding of how C. elegans responds metabolically to complex I inhibition via multiple bioenergetic adaptations, including the glyoxylate pathway, will be useful in interrogating the effects of mitochondrial and bioenergetic stressors and toxicants.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.