Journal article
Cardiac ryanodine receptor (Ryr2)-mediated calcium signals specifically promote glucose oxidation via pyruvate dehydrogenase
MJ Bround, R Wambolt, H Cen, P Asghari, RF Albu, J Han, D McAfee, M Pourrier, NE Scott, L Bohunek, JE Kulpa, SRW Chen, D Fedida, RW Brownsey, CH Borchers, LJ Foster, T Mayor, EDW Moore, MF Allard, JD Johnson
Journal of Biological Chemistry | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 2016
Abstract
Cardiac ryanodine receptor (Ryr2) Ca2+ release channels and cellular metabolism are both disrupted in heart disease. Recently, we demonstrated that total loss of Ryr2 leads to cardiomyocyte contractile dysfunction, arrhythmia, and reduced heart rate. Acute total Ryr2 ablation also impaired metabolism, but it was not clear whether this was a cause or consequence of heart failure. Previous in vitro studies revealed that Ca2+ flux into the mitochondria helps pace oxidative metabolism, but there is limited in vivo evidence supporting this concept. Here, we studied heart-specific, inducible Ryr2 haploinsufficient (cRyr2Δ50) mice with a stable 50% reduction in Ryr2 protein. This manipulation decre..
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Awarded by Canadian Institutes of Health Research (CIHR)
Funding Acknowledgements
This work was supported by University of British Columbia Start-Up Funds (to J. D. J.), funding from the Canadian Institutes of Health Research (CIHR) (MOP-77688) (to L. J. F.) and (MOP 115158) (to E. D. W. M.), a scholarship from CIHR (to M. J. B.), a scholarship from the Michael Smith Foundation for Health Research (to N. E. S.), and Natural Sciences and Engineering Research Council of Canada (NSERC) and the Heart and Stroke Foundation/Libin Cardiovascular Institute Professorship in Cardiovascular Research (to S. R. W. C.). The authors declare that they have no conflicts of interest with the contents of this article.