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From the Cover: Arsenite Uncouples Mitochondrial Respiration and Induces a Warburg-like Effect in Caenorhabditis elegans.

Publication ,  Journal Article
Luz, AL; Godebo, TR; Bhatt, DP; Ilkayeva, OR; Maurer, LL; Hirschey, MD; Meyer, JN
Published in: Toxicol Sci
August 2016

Millions of people worldwide are chronically exposed to arsenic through contaminated drinking water. Despite decades of research studying the carcinogenic potential of arsenic, the mechanisms by which arsenic causes cancer and other diseases remain poorly understood. Mitochondria appear to be an important target of arsenic toxicity. The trivalent arsenical, arsenite, can induce mitochondrial reactive oxygen species production, inhibit enzymes involved in energy metabolism, and induce aerobic glycolysis in vitro, suggesting that metabolic dysfunction may be important in arsenic-induced disease. Here, using the model organism Caenorhabditis elegans and a novel metabolic inhibition assay, we report an in vivo induction of aerobic glycolysis following arsenite exposure. Furthermore, arsenite exposure induced severe mitochondrial dysfunction, including altered pyruvate metabolism; reduced steady-state ATP levels, ATP-linked respiration and spare respiratory capacity; and increased proton leak. We also found evidence that induction of autophagy is an important protective response to arsenite exposure. Because these results demonstrate that mitochondria are an important in vivo target of arsenite toxicity, we hypothesized that deficiencies in mitochondrial electron transport chain genes, which cause mitochondrial disease in humans, would sensitize nematodes to arsenite. In agreement with this, nematodes deficient in electron transport chain complexes I, II, and III, but not ATP synthase, were sensitive to arsenite exposure, thus identifying a novel class of gene-environment interactions that warrant further investigation in the human populace.

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Published In

Toxicol Sci

DOI

EISSN

1096-0929

Publication Date

August 2016

Volume

152

Issue

2

Start / End Page

349 / 362

Location

United States

Related Subject Headings

  • Toxicology
  • Pyruvic Acid
  • Pyruvate Dehydrogenase Complex
  • Oxygen Consumption
  • Mutation
  • Mitochondria
  • Metabolomics
  • Membrane Potential, Mitochondrial
  • Mass Spectrometry
  • Glycolysis
 

Citation

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Luz, A. L., Godebo, T. R., Bhatt, D. P., Ilkayeva, O. R., Maurer, L. L., Hirschey, M. D., & Meyer, J. N. (2016). From the Cover: Arsenite Uncouples Mitochondrial Respiration and Induces a Warburg-like Effect in Caenorhabditis elegans. Toxicol Sci, 152(2), 349–362. https://doi.org/10.1093/toxsci/kfw093
Luz, Anthony L., Tewodros R. Godebo, Dhaval P. Bhatt, Olga R. Ilkayeva, Laura L. Maurer, Matthew D. Hirschey, and Joel N. Meyer. “From the Cover: Arsenite Uncouples Mitochondrial Respiration and Induces a Warburg-like Effect in Caenorhabditis elegans.Toxicol Sci 152, no. 2 (August 2016): 349–62. https://doi.org/10.1093/toxsci/kfw093.
Luz AL, Godebo TR, Bhatt DP, Ilkayeva OR, Maurer LL, Hirschey MD, et al. From the Cover: Arsenite Uncouples Mitochondrial Respiration and Induces a Warburg-like Effect in Caenorhabditis elegans. Toxicol Sci. 2016 Aug;152(2):349–62.
Luz, Anthony L., et al. “From the Cover: Arsenite Uncouples Mitochondrial Respiration and Induces a Warburg-like Effect in Caenorhabditis elegans.Toxicol Sci, vol. 152, no. 2, Aug. 2016, pp. 349–62. Pubmed, doi:10.1093/toxsci/kfw093.
Luz AL, Godebo TR, Bhatt DP, Ilkayeva OR, Maurer LL, Hirschey MD, Meyer JN. From the Cover: Arsenite Uncouples Mitochondrial Respiration and Induces a Warburg-like Effect in Caenorhabditis elegans. Toxicol Sci. 2016 Aug;152(2):349–362.
Journal cover image

Published In

Toxicol Sci

DOI

EISSN

1096-0929

Publication Date

August 2016

Volume

152

Issue

2

Start / End Page

349 / 362

Location

United States

Related Subject Headings

  • Toxicology
  • Pyruvic Acid
  • Pyruvate Dehydrogenase Complex
  • Oxygen Consumption
  • Mutation
  • Mitochondria
  • Metabolomics
  • Membrane Potential, Mitochondrial
  • Mass Spectrometry
  • Glycolysis