PUBLICATION
Loss of dihydrolipoyl succinyltransferase (DLST) leads to reduced resting heart rate in the zebrafish
- Authors
- Keßler, M., Berger, I.M., Just, S., Rottbauer, W.
- ID
- ZDB-PUB-150224-21
- Date
- 2015
- Source
- Basic Research in Cardiology 110: 468 (Journal)
- Registered Authors
- Berger, Ina, Just, Steffen, Keßler, Mirjam, Rottbauer, Wolfgang
- Keywords
- none
- MeSH Terms
-
- Acyltransferases/genetics
- Acyltransferases/metabolism*
- Animals
- Gene Knockdown Techniques
- Heart Rate/physiology*
- Real-Time Polymerase Chain Reaction
- Zebrafish
- PubMed
- 25697682 Full text @ Basic Res. Cardiol.
Citation
Keßler, M., Berger, I.M., Just, S., Rottbauer, W. (2015) Loss of dihydrolipoyl succinyltransferase (DLST) leads to reduced resting heart rate in the zebrafish. Basic Research in Cardiology. 110:468.
Abstract
The genetic underpinnings of heart rate regulation are only poorly understood. In search for genetic regulators of cardiac pacemaker activity, we isolated in a large-scale mutagenesis screen the embryonic lethal, recessive zebrafish mutant schneckentempo (ste). Homozygous ste mutants exhibit a severely reduced resting heart rate with normal atrio-ventricular conduction and contractile function. External electrical pacing reveals that defective excitation generation in cardiac pacemaker cells underlies bradycardia in ste (-/-) mutants. By positional cloning and gene knock-down analysis we find that loss of dihydrolipoyl succinyltransferase (DLST) function causes the ste phenotype. The mitochondrial enzyme DLST is an essential player in the citric acid cycle that warrants proper adenosine-tri-phosphate (ATP) production. Accordingly, ATP levels are significantly diminished in ste (-/-) mutant embryos, suggesting that limited energy supply accounts for reduced cardiac pacemaker activity in ste (-/-) mutants. We demonstrate here for the first time that the mitochondrial enzyme DLST plays an essential role in the modulation of the vertebrate heart rate by controlling ATP production in the heart.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping