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Molecular and Cellular Biology, June 2007, p. 4365-4373, Vol. 27, No. 12
0270-7306/07/$08.00+0     doi:10.1128/MCB.02045-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

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

Melanie Boerries,1,2,{dagger} Patrick Most,3,4,{dagger} Jonathan R. Gledhill,5 John E. Walker,5 Hugo A. Katus,4 Walter J. Koch,3 Ueli Aebi,1 and Cora-Ann Schoenenberger1*

Maurice E. Mueller Institute, Biozentrum, University of Basel, 4056 Basel, Switzerland,1 Institute for Pharmacology and Toxicology, University of Freiburg, 79104 Freiburg, Germany,2 Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107,3 Department of Internal Medicine III, Division of Cardiology, University of Heidelberg, 69115 Heidelberg, Germany,4 Medical Research Council Dunn Human Nutrition Unit, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 2XY, United Kingdom5

Received 2 November 2006/ Returned for modification 9 January 2007/ Accepted 5 April 2007

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 {alpha}- and ß-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.

* Corresponding author. Mailing address: Maurice E. Mueller Institute for Structural Biology, Biozentrum, University of Basel, 4056 Basel, Switzerland. Phone: 0041-612672096. Fax: 0041-612672109. E-mail: cora-ann.schoenenberger{at}unibas.ch

{triangledown} Published ahead of print on 16 April 2007.

{dagger} These authors contributed equally to this study.

Molecular and Cellular Biology, June 2007, p. 4365-4373, Vol. 27, No. 12
0270-7306/07/$08.00+0     doi:10.1128/MCB.02045-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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  • Most, P., Remppis, A., Pleger, S. T., Katus, H. A., Koch, W. J. (2007). S100A1: a novel inotropic regulator of cardiac performance. Transition from molecular physiology to pathophysiological relevance. Am. J. Physiol. Regul. Integr. Comp. Physiol. 293: R568-R577 [Abstract] [Full Text]  


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