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Ca2+ -dependent interaction of S100A1 with F1-ATPase leads to an increased ATP content in cardiomyocytes

Boerries, Melanie and Most, Patrick and Gledhill, Jonathan R. and Walker, John E. and Katus, Hugo A. and Koch, Walter J. and Aebi, Ueli and Schoenenberger, Cora-Ann. (2007) Ca2+ -dependent interaction of S100A1 with F1-ATPase leads to an increased ATP content in cardiomyocytes. Molecular and cellular biology, Vol. 27, H. 12. pp. 4365-4373.

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Official URL: http://edoc.unibas.ch/dok/A5259479

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Abstract

S100A1, a Ca(2+)-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 Ca(2+) homeostasis, S100A1 was able to rescue contractile dysfunction in failing rat hearts. Myocardial contractility is regulated not only by Ca(2+) homeostasis but also by energy metabolism, in particular the production of ATP. Here, we report a novel interaction of S100A1 with mitochondrial F(1)-ATPase, which affects F(1)-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 beta-chain of F(1)-ATPase to interact with S100A1 in a Ca(2+)-dependent manner. The interaction was confirmed by colocalization studies of S100A1 and F(1)-ATPase and the analysis of the S100A1-F(1)-ATPase complex by gel filtration chromatography. The functional impact of this association is highlighted by an S100A1-mediated increase of F(1)-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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Structural Biology (Aebi)
05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Structural Biology (Schoenenberger)
UniBasel Contributors:Schoenenberger, Cora-Ann and Aebi, Ueli
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Society for Microbiology
ISSN:1098-5549
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:04 Jan 2013 08:35
Deposited On:22 Mar 2012 13:22

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