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Ca2+-Dependent Interaction of S100A1 with F1-ATPase Leads to an Increased ATP Content in Cardiomyocytes

  • Boerries, Melanie Institute for Pharmacology and Toxicology, University of Freiburg, 79104 Freiburg, Germany
  • Most, Patrick Department of Internal Medicine III, Division of Cardiology, University of Heidelberg, 69115 Heidelberg, Germany
  • Gledhill, Jonathan R. Medical Research Council Dunn Human Nutrition Unit, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 2XY, United Kingdom
  • Walker, John E. Medical Research Council Dunn Human Nutrition Unit, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 2XY, United Kingdom
  • Katus, Hugo A. Department of Internal Medicine III, Division of Cardiology, University of Heidelberg, 69115 Heidelberg, Germany
  • Koch, Walter J. Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107
  • Aebi, Ueli Maurice E. Mueller Institute, Biozentrum, University of Basel, 4056 Basel, Switzerland
  • Schoenenberger, Cora-Ann Maurice E. Mueller Institute, Biozentrum, University of Basel, 4056 Basel, Switzerland
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Published in:
  • Molecular and Cellular Biology. - American Society for Microbiology. - 2007, vol. 27, no. 12, p. 4365-4373
Cell Biology
Molecular Biology
English ABSTRACT
S100A1, a Ca2+-sensing protein of the EF-hand family that is expressed predominantly in cardiac muscle, plays a pivotal role in cardiac contractility in vitro and in vivo. It has recently been demonstrated that by restoring Ca2+ homeostasis, S100A1 was able to rescue contractile dysfunction in failing rat hearts. Myocardial contractility is regulated not only by Ca2+ homeostasis but also by energy metabolism, in particular the production of ATP. Here, we report a novel interaction of S100A1 with mitochondrial F1-ATPase, which affects F1-ATPase activity and cellular ATP production. In particular, cardiomyocytes that overexpress S100A1 exhibited a higher ATP content than control cells, whereas knockdown of S100A1 expression decreased ATP levels. In pull-down experiments, we identified the α- and β-chain of F1-ATPase to interact with S100A1 in a Ca2+-dependent manner. The interaction was confirmed by colocalization studies of S100A1 and F1-ATPase and the analysis of the S100A1-F1-ATPase complex by gel filtration chromatography. The functional impact of this association is highlighted by an S100A1-mediated increase of F1-ATPase activity. Consistently, ATP synthase activity is reduced in cardiomyocytes from S100A1 knockout mice. Our data indicate that S100A1 might play a key role in cardiac energy metabolism.
Language
  • English
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bronze
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https://sonar.ch/global/documents/5556
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