REGULATION OF MITOCHONDRIAL ATP SYNTHASE ACTIVITY IN HUMAN MYOCARDIUM

1. In previous studies regulation of the F0F1-ATPase of mitochondrial complex V (ATP synthase) has been demonstrated in rat cardiomyocytes, canine mycocardium and skeletal muscle from children, The aim of the p resent study was to examine regulation of ATP synthase in human myocar dium in response to different metabolic states. 2. Biopsy material was obtained from 10 children undergoing cardiac surgery. Mitochondria in the postnuclear supernatant were incubated under different metabolic conditions for 15 min and then broken by sonication, ATP synthase was measured spectrophotometrically using a coupled enzyme assay. 3. ATP s ynthase can be rapidly measured in sonicated preparations of heart mit ochondria from children. We show that direct regulation at the level o f ATP synthase occurs in these mitochondria. ATP synthase capacity is decreased in response to blocking of the respiratory chain by cyanide (mimicking anoxia) or uncoupling of mitochondria, falling to 76 % and 66 % of control values respectively. Upregulation of ATP synthase can be demonstrated in heart mitochondria when the calcium concentration i n the incubation medium is increased to 5 mu M (130 % of control). 4. ATP synthase is actively regulated in heart mitochondria from children . The enzyme is upregulated in response to increased calcium. This tra nsition may reflect the increased energy demand when cardiac workload is increased.