Regulation of the mitochondrial ATP synthase in intact rat cardiomyocytes

Abstract

The ATP synthase capacity of rat heart myocytes can be measured in sonicated cell suspensions and in sonicated preparations of cultured cardiomyocytes. This procedure allows the rapid measurement of mitochondrial function in response to changes in the metabolic status of the cell. In cultured myocytes, transitions in ATP synthase capacity (with no detectable change in cellular ATP concentration) accompany a change to anoxia or electrically stimulated contraction (rise of 70%). These changes are reversed on returning to the original conditions. Exposure of myocytes to low pH has little effect on basal ATP synthase capacity (down to values less than pH 6), but markedly affects cellular ATP levels and the response of the cells to anoxia and reoxygenation, possibly mimicking changes seen in ischaemic heart. Similar effects are seen in suspensions of freshly prepared myocytes, but these preparations are less stable and more pH-sensitive than are cells in culture. It is proposed that mitochondria in vivo are directly regulated at the level of the ATP synthase, and that a regulator protein, the naturally occurring inhibitor protein from mitochondria, may be responsible for this regulation.

Amyloid precursor protein and amyloid β-peptide bind to ATP synthase and regulate its activity at the surface of neural cells

“…37 Electrophysiological recordings Two-to three-month-old C57Bl/6J mice of both sexes were used for the electrophysiological experiments. Hippocampal slice preparation and recordings of long-term potentiation (LTP) at CA3-CA1 synapses were performed as described elsewhere.…”

F0F1ATP synthase activity is differently modulated by coronary reactive hyperemia before and after ischemic preconditioning in the goat

“…coronary circulation; energy metabolism; ischemia; mitochondria THE IMMEDIATE SOURCE OF ENERGY for myocardial contraction is provided by the hydrolysis of ATP. Although ATP hydrolysis is carried out by a number of ATPases, its resynthesis is mainly mediated by mitochondrial F 0 F 1 ATP synthase, which couples the transport of protons across the mitochondrial inner membrane to the synthesis of ATP (6,7,12). However, when the proton electrochemical gradient across the inner membrane collapses, the enzyme switches its catalytic activity from ATP synthesis to ATP hydrolysis (12).…”

Mitochondrial ATP hydrolysis and ATP depletion in thymocytes and Ehrlich ascites carcinoma cells

“…The fraction of de-energized mitochondria in thymocytes and in EAC cells is very small both at high and low rate of glycolysis. It is interesting to compare these results with the data on mitochondrial ATPase regulation in cardiomyocytes [8]. In the resting cardiomyocytes approximately 50% of ATPase is blocked and can be activated upon electrical stimulation of the cells.…”

“…IF, is unable to block more than 30% of ATPase in mitochondria from rat liver, but inhibits ATPase completely in rapidly growing hepatoma [5,7]. The regulation of mitochondrial ATPase in intact cells was studied in experiments with rat cardiomyocytes [8]. It was shown that uncoupler or inhibitors of respiration *Corresponding author.…”