Stimulatory effects of calcium on respiration and NAD(P)H synthesis in intact rat heart mitochondria utilizing physiological substrates cannot explain respiratory control in vivo. J Biol Chem 2011 Sep 02;286(35):30816-30822
Date
07/16/2011Pubmed ID
21757763Pubmed Central ID
PMC3162442DOI
10.1074/jbc.M111.242529Scopus ID
2-s2.0-80052210048 (requires institutional sign-in at Scopus site) 22 CitationsAbstract
Mitochondrial TCA cycle dehydrogenase enzymes have been shown to be stimulated by Ca(2+) under various substrate and ADP incubation conditions in an attempt to determine and understand the role of Ca(2+) in maintaining energy homeostasis in working hearts. In this study, we tested the hypothesis that, at physiological temperature and 1 mM extramitochondrial free magnesium, Ca(2+) can stimulate the overall mitochondrial NAD(P)H generation flux in rat heart mitochondria utilizing pyruvate and malate as substrates at both subsaturating and saturating concentrations. In both cases, we found that, in the physiological regime of mitochondrial oxygen consumption observed in the intact animal and in the physiological range of cytosolic Ca(2+) concentration averaged per beat, Ca(2+) had no observable stimulatory effect. A modest apparent stimulatory effect (22-27%) was observable at supraphysiological maximal ADP-stimulated respiration at 2.5 mM initial phosphate. The stimulatory effects observed over the physiological Ca(2+) range are not sufficient to make a significant contribution to the control of oxidative phosphorylation in the heart in vivo.
Author List
Vinnakota KC, Dash RK, Beard DAAuthor
Ranjan K. Dash PhD Professor in the Biomedical Engineering department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adenosine DiphosphateAnimals
Calcium
Cell Respiration
Dose-Response Relationship, Drug
Ketoglutaric Acids
Malates
Mitochondria, Heart
NAD
NADP
Oxidative Phosphorylation
Oxygen
Phosphorylation
Protein Binding
Rats
Tricarboxylic Acids
