PUBLICATION

Long-Chain Acyl-Carnitines Interfere with Mitochondrial ATP Production Leading to Cardiac Dysfunction in Zebrafish

Authors
Park, D.D., Gahr, B.M., Krause, J., Rottbauer, W., Zeller, T., Just, S.
ID
ZDB-PUB-210828-35
Date
2021
Source
International Journal of Molecular Sciences   22(16): (Journal)
Registered Authors
Gahr, Bernd, Just, Steffen, Park, Deung-Dae, Rottbauer, Wolfgang
Keywords
cardiovascular disease, long-chain acylcarnitine, mitochondria, zebrafish
MeSH Terms
  • Carnitine/analogs & derivatives*
  • Carnitine/metabolism
  • Fatty Acids/metabolism*
  • Disease Models, Animal
  • Heart/physiopathology
  • Animals
  • Mitochondria, Heart/metabolism*
  • Mitochondria, Heart/pathology
  • Myocytes, Cardiac/metabolism
  • Myocytes, Cardiac/pathology
  • Adenosine Triphosphate/metabolism*
  • Zebrafish*/embryology
  • Zebrafish*/metabolism
  • Zebrafish*/physiology
  • Heart Diseases/metabolism*
  • Heart Diseases/pathology
  • Oxidation-Reduction
  • Humans
(all 18)
PubMed
34445174 Full text @ Int. J. Mol. Sci.
Abstract
In the human heart, the energy supplied by the production of ATP is predominately accomplished by ß-oxidation in mitochondria, using fatty acids (FAs) as the primary fuel. Long-chain acylcarnitines (LCACs) are intermediate forms of FA transport that are essential for FA delivery from the cytosol into mitochondria. Here, we analyzed the impact of the LCACs C18 and C18:1 on mitochondrial function and, subsequently, on heart functionality in the in vivo vertebrate model system of zebrafish (Danio rerio). Since LCACs are formed and metabolized in mitochondria, we assessed mitochondrial morphology, structure and density in C18- and C18:1-treated zebrafish and found no mitochondrial alterations compared to control-treated (short-chain acylcarnitine, C3) zebrafish embryos. However, mitochondrial function and subsequently ATP production was severely impaired in C18- and C18:1-treated zebrafish embryos. Furthermore, we found that C18 and C18:1 treatment of zebrafish embryos led to significantly impaired cardiac contractile function, accompanied by reduced heart rate and diminished atrial and ventricular fractional shortening, without interfering with cardiomyocyte differentiation, specification and growth. In summary, our findings provide insights into the direct role of long-chain acylcarnitines on vertebrate heart function by interfering with regular mitochondrial function and thereby energy allocation in cardiomyocytes.
Genes / Markers
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Allele Construct Type Affected Genomic Region
f2TgTransgenic Insertion
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    DsRed2EFGDsRed2
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    Citation
    Park, D.D., Gahr, B.M., Krause, J., Rottbauer, W., Zeller, T., Just, S. (2021) Long-Chain Acyl-Carnitines Interfere with Mitochondrial ATP Production Leading to Cardiac Dysfunction in Zebrafish. International Journal of Molecular Sciences. 22(16):.