Control of mitochondrial ATP synthase in rat cardiomyocytes: effects of thyroid hormone.
Activities of the mitochondrial ATP synthase and the electron transfer chain were investigated in cultured cardiomyocytes prepared from untreated and thyroxine-treated rats. Quiescent cells from the thyroxine-treated animals showed a 33% increase in mitochondrial ATP synthase capacity, but no change in respiratory chain capacity, relative to those from control animals. This increase was attributable largely to (a) a 25% increase in F1 content in these mitochondria, and partly to (b) a 10% stimulation in ATPase activity due to raised intramitochondrial Ca2+. Both types of cell showed a normal ATP content of 38-40 nmol/mg cell protein. In control cells, the mitochondrial ATP synthase responded to increased energy demand (by electrical stimulation and/or by positive inotropic agents) with an increase in its capacity of up to 2-fold. This response was absent in cells from thyroxine-treated animals. In addition, cellular ATP levels fell significantly after 2 min electrical stimulation of cells from thyroxine-treated animals, while those of control cells were constant. It was concluded that regulation of the mitochondrial ATP synthase was defective in heart cells from thyroxine treated rats, leading to an energy deficit when energy demand on the cells was increased. Animals treated with thyroxine, but allowed to recover for 17 days after treatment, showed responses indistinguishable from the control cells. Thus, the effects of thyroxine on mitochondrial activities were reversible.
Das
A M
AM
Department of Biochemistry, Oxford, U.K.
Harris
D A
DA
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D006980:Hyperthyroidism / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D009206:Myocardium / Q000166:cytology / Q000201:enzymology*; D006180:Proton-Translocating ATPases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013974:Thyroxine / Q000502:physiology*
D000255:Adenosine Triphosphate; D006180:Proton-Translocating ATPases; D013974:Thyroxine