Bioenergetic Profiling of Zebrafish Embryonic Development

Many debilitating conditions are linked to bioenergetic defects. Developing screens to probe the genetic and/or chemical basis for such links has proved intractable. Furthermore, there is a need for a physiologically relevant assay of bioenergetics in whole organisms, especially for early stages in life where perturbations could increase disease susceptibility with aging. Thus, we asked whether we could screen bioenergetics and mitochondrial function in the developing zebrafish embryo. We present a multiplexed method to assay bioenergetics in zebrafish embryos from the blastula period (3 hours post-fertilization, hpf) through to hatching (48 hpf). In proof of principle experiments, we measured respiration and acid extrusion of developing zebrafish embryos. We quantified respiratory coupling to various bioenergetic functions by using specific pharmacological inhibitors of bioenergetic pathways. We demonstrate that changes in the coupling to ATP turnover and proton leak are correlated with developmental stage. The multiwell format of this assay enables the user to screen for the effects of drugs and environmental agents on bioenergetics in the zebrafish embryo with high sensitivity and reproducibility.

• Publication year

  2011

• Venue

  PLoS ONE

• Publication date

  2011-09-29

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1371/journal.pone.0025652PMID 21980518PMCID 3183059
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2010cited by this paper
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  2010cited by this paper
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  2010cited by this paper
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  2010cited by this paper
• Quantitative Microplate-Based Respirometry with Correction for Oxygen Diffusion

  2009cited by this paper
• The Relationship Between Pluripotency and Mitochondrial DNA Proliferation During Early Embryo Development and Embryonic Stem Cell Differentiation

  2009cited by this paper
• Mitochondria in early mammalian development.

  2009cited by this paper
• Bioenergetic analysis of isolated cerebrocortical nerve terminals on a microgram scale: spare respiratory capacity and stochastic mitochondrial failure

  2009influential reference
• Bmi1 regulates mitochondrial function and the DNA damage response pathway

  2009cited by this paper
• AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity

  2009cited by this paper
• Coordination of development and metabolism in the pre‐midblastula transition zebrafish embryo

  2008cited by this paper
• Zebrafish: a predictive model for assessing drug-induced toxicity.

  2008cited by this paper
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  2008cited by this paper
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  2007cited by this paper
• Strategies to reduce late-stage drug attrition due to mitochondrial toxicity

  2007cited by this paper
• The significance of mitochondrial toxicity testing in drug development.

  2007cited by this paper
• Mitochondrial toxicity in hearts of CD‐1 mice following perinatal exposure to AZT, 3TC, or AZT/3TC in combination

  2007cited by this paper
• Mitochondrial disease.

  2006cited by this paper
• Carbohydrate metabolism of eggs of the whitefish, Coregonus spp. during embryogenesis and its relationship with egg quality.

  2005cited by this paper
• In vivo drug discovery in the zebrafish

  2005cited by this paper
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  2005cited by this paper
• The efficiency and plasticity of mitochondrial energy transduction.

  2005cited by this paper
• Metabolic responses to low temperature in fish muscle

  2004cited by this paper
• Cell surface oxygen consumption by mitochondrial gene knockout cells.

  2004cited by this paper
• Individual variation in the rate of oxygen consumption by zebrafish embryos

  2004cited by this paper
• Characterization of embryonic globin genes of the zebrafish.

  2003cited by this paper
• Zebrafish-based small molecule discovery.

  2003cited by this paper
• Zebrafish: A Preclinical Model for Drug Screening

  2002cited by this paper
• Influence of hypoxia and of hypoxemia on the development of cardiac activity in zebrafish larvae.

  2002cited by this paper
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  2000cited by this paper
• Tetrahydrobiopterin Regulates Cyclic GMP‐Dependent Electrogenic Cl− Secretion in Mouse Ileum In Vitro

  1997cited by this paper
• The Physiological Significance of Mitochondrial Proton Leak in Animal Cells and Tissues

  1997cited by this paper
• Copyright � 1997, American Society for Microbiology Transcription-Dependent Induction of G 1 Phase during the Zebra Fish Midblastula Transition

  1996cited by this paper
• The zebrafish book : a guide for the laboratory use of zebrafish (Danio rerio)

  1995cited by this paper
• Early life history of fish: An energetics approach

  1995cited by this paper
• Stages of embryonic development of the zebrafish

  1995cited by this paper
• 12 – Measurement of Oxygen Consumption

  1994cited by this paper
• Fish Farming Technology

  1993cited by this paper
• Evolution of energy metabolism. Proton permeability of the inner membrane of liver mitochondria is greater in a mammal than in a reptile.

  1991cited by this paper
• Sexual expression in paraplegia.

  1991cited by this paper
• 6 Yolk Absorption in Embryonic and Larval Fishes

  1988cited by this paper
• Gene expression in Xenopus embryogenesis.

  1985influential reference
• Spectrophotometric assay for D-(-)-lactate in plasma.

  1980cited by this paper

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