Cardiovascular Research, 1990, 24, 41 1-417
41 1
Control of mitochondrial ATP synthase in heart cells: inactive to active transitions caused by beating or positive inotropic agents Anibh M Das, David A Harris
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom A M Das D A Harris Correspondence to: Dr Harris Key words: mitochondria; cardiomyocytes; ATP synthase; metabolic regulation; calcium ions; isoprenaline; p blocker; anoxia. Submitted 24 Jury 1989 Accepted 18 December 1989
As the workload of the heart increases, mitochondrial ATP synthesis must rise to match ATP utilisation. It is generally believed that mitochondrial respiration is “controlled” by substrate levels, higher ADP levels leading to a higher degree of saturation of the ATP synthase. This model has, however, been questioned. First, 31P NMR studies of the in situ heart’ or of perfused heart preparationss5 have not shown changes in nucleotide levels with increased ,rates of oxygen consumption. Secondly, the ATP synthase in heart mitochondria has been shown to be a potential control site, since it has a significant control strength at physiological rates of ATP synthesis.6 Thirdly, the ATP synthase in submitochondrial vesicles has been shown to be regulated by a variety of elements, in particular the naturally occurring inhibitor protein,
’
IF’.’ * Regulation at the level of the ATP synthase would require changes in turnover number (“capacity”) or affinity of the enzyme for its substrate. To detect such changes in vivo is difficult, requiring either non-invasive studies of mitochondrial activities, or a procedure for “freezing” the activated state of the ATP synthase during isolation and assay. We have developed a method for rapid (
41 1
Control of mitochondrial ATP synthase in heart cells: inactive to active transitions caused by beating or positive inotropic agents Anibh M Das, David A Harris
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom A M Das D A Harris Correspondence to: Dr Harris Key words: mitochondria; cardiomyocytes; ATP synthase; metabolic regulation; calcium ions; isoprenaline; p blocker; anoxia. Submitted 24 Jury 1989 Accepted 18 December 1989
As the workload of the heart increases, mitochondrial ATP synthesis must rise to match ATP utilisation. It is generally believed that mitochondrial respiration is “controlled” by substrate levels, higher ADP levels leading to a higher degree of saturation of the ATP synthase. This model has, however, been questioned. First, 31P NMR studies of the in situ heart’ or of perfused heart preparationss5 have not shown changes in nucleotide levels with increased ,rates of oxygen consumption. Secondly, the ATP synthase in heart mitochondria has been shown to be a potential control site, since it has a significant control strength at physiological rates of ATP synthesis.6 Thirdly, the ATP synthase in submitochondrial vesicles has been shown to be regulated by a variety of elements, in particular the naturally occurring inhibitor protein,
’
IF’.’ * Regulation at the level of the ATP synthase would require changes in turnover number (“capacity”) or affinity of the enzyme for its substrate. To detect such changes in vivo is difficult, requiring either non-invasive studies of mitochondrial activities, or a procedure for “freezing” the activated state of the ATP synthase during isolation and assay. We have developed a method for rapid (
