Regulation of the mitochondrial ATP synthase is defective in rat heart during alcohol-induced cardiomyopathy.
Mitochondrial ATP synthase capacity was measured in cardiomyocytes from sucrose-fed (control) and alcohol-fed (cardiomyopathic) rats. Cells from alcohol-fed rats showed an ATP synthase capacity raised by 40% relative to the control values of 1.8 mumol/min per mg cell protein. Cells from control rats were able to increase their ATP synthase capacity by up to 80% in response to increased energy demand. In contrast, cells from alcohol-fed rats had lost the ability to up-regulate their ATP synthase. Cells from control rats maintained their internal ATP levels at 38 nmol/mg cell protein before and after an increased energy demand. In cells from alcohol-fed rats, ATP levels fell by 20% after 2 min of increased energy demand. It was concluded that the inability of cells from alcohol-fed rats to maintain ATP levels was due to their reduced ability to increase mitochondrial ATP synthase activity as energy demand is increased. Such ATP deficits may contribute to heart dysfunction in alcohol-induced cardiomyopathy.
Das
A M
AM
Department of Biochemistry, University of Oxford, UK.
Harris
D A
DA
D025181:ATP Synthetase Complexes; D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D002310:Cardiomyopathy, Alcoholic / Q000378:metabolism*; D002478:Cells, Cultured; D003486:Cyanides; D015536:Down-Regulation; D004558:Electric Stimulation; D007545:Isoproterenol; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology*; D006180:Proton-Translocating ATPases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D003486:Cyanides; D000255:Adenosine Triphosphate; D025181:ATP Synthetase Complexes; D006180:Proton-Translocating ATPases; D007545:Isoproterenol