ZFIN ID: ZDB-PUB-080908-5
At environmental doses, dietary methylmercury inhibits mitochondrial energy metabolism in skeletal muscles of the zebra fish (Danio rerio)
Cambier, S., Bénard, G., Mesmer-Dudons, N., Gonzalez, P., Rossignol, R., Brèthes, D., and Bourdineaud, J.P.
Date: 2009
Source: The international journal of biochemistry & cell biology   41(4): 791-799 (Journal)
Registered Authors:
Keywords: Danio rerio, Zebrafish, Methylmercury, Mitochondria, Electron transfer chain, ATP synthesis, Complex IV
MeSH Terms:
  • Adenosine Triphosphate/biosynthesis
  • Adenosine Triphosphate/metabolism
  • Animals
  • Cell Respiration/drug effects
  • Electron Transport/drug effects
  • Electron Transport Complex IV/metabolism
  • Energy Metabolism/drug effects
  • Gene Expression/drug effects
  • Male
  • Methylmercury Compounds/toxicity*
  • Microscopy, Electron, Transmission
  • Mitochondria/drug effects*
  • Mitochondria/enzymology
  • Mitochondria/metabolism
  • Mitochondria/ultrastructure
  • Mitochondrial Proton-Translocating ATPases/biosynthesis
  • Mitochondrial Proton-Translocating ATPases/genetics
  • Muscle, Skeletal/drug effects*
  • Muscle, Skeletal/enzymology
  • Muscle, Skeletal/metabolism
  • NADH Dehydrogenase/biosynthesis
  • NADH Dehydrogenase/genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Zebrafish/metabolism*
PubMed: 18765295 Full text @ Int. J. Biochem. Cell Biol.
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ABSTRACT
The neurotoxic compound methylmercury (MeHg) is a commonly encountered pollutant in the environment, and constitutes a hazard for human health through fish eating. To study the impact of MeHg on mitochondrial structure and function, we contaminated the model fish species Danio rerio with food containing 13mug of MeHg per gram, an environmentally relevant dose. Mitochondria from contaminated zebrafish muscles presented structural abnormalities under electron microscopy observation. In permeabilized muscle fibers, we observed, a strong inhibition of both state 3 mitochondrial respiration and functionally isolated maximal cytochrome c oxidase (COX) activity after 49 days of MeHg exposure. However, the state 4 respiratory rate remained essentially unchanged. This suggested a defect at the level of ATP synthesis. Accordingly, we measured a dramatic decrease in the rate of ATP release by skinned muscle fibers using either pyruvate and malate or succinate as respiratory substrates. However, the amount and the assembly of the ATP synthase were identical in both control and contaminated muscle mitochondrial fractions. This suggests that MeHg induced a decoupling of mitochondrial oxidative phosphorylation in the skeletal muscle of zebrafish. Western blot analysis showed a 30% decrease of COX subunit IV levels, a 50% increase of ATP synthase subunit alpha, and a 40% increase of the succinate dehydrogenase Fe/S protein subunit in the contaminated muscles. This was confirmed by the analysis of gene expression levels, using RT-PCR. Our study provides a basis for further analysis of the deleterious effect of MeHg on fish health via mitochondrial impairment.
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