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

TitleCa2+ -dependent interaction of S100A1 with F1-ATPase leads to an increased ATP content in cardiomyocytes.
Publication TypeJournal Article
Year of Publication2007
AuthorsBoerries, M, Most, P, Gledhill, JR, Walker, JE, Katus, HA, Koch, WJ, Aebi, U, Schoenenberger, C-A
JournalMol Cell Biol
Volume27
Issue12
Pagination4365-73
Date Published2007 Jun
ISSN0270-7306
KeywordsAdenosine Triphosphate, Adenoviridae, Animals, Calcium, Cells, Cultured, Fluorescent Antibody Technique, Indirect, Genes, Reporter, Glutathione Transferase, Green Fluorescent Proteins, Heart Ventricles, Luciferases, Mice, Mice, Inbred C57BL, Mice, Knockout, Mitochondria, Heart, Myocytes, Cardiac, Proton-Translocating ATPases, Recombinant Fusion Proteins, RNA Interference, S100 Proteins
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.

DOI10.1128/MCB.02045-06
Alternate JournalMol. Cell. Biol.
Citation Key10.1128/MCB.02045-06
PubMed ID17438143
PubMed Central IDPMC1900044
Grant ListMC_U105663150 / / Medical Research Council / United Kingdom