REGULATION OF THE MITOCHONDRIAL ATP-SYNTHASE IN HUMAN FIBROBLASTS

The F1F0-ATPase activity of mitochondrial complex V can be rapidly mea sured in sonicated preparations of monolayer skin fibroblast cultures from children. We show that direct regulation at the level of ATP-synt hase occurs in these cell preparations. ATP-synthase capacity is decre ased in response to blocking of the respiratory chain by cyanide (mimi cking anoxia) or uncoupling of mitochondria. ATP-synthase capacity fal ls to 60% and 35% of control, respectively. Up-regulation of ATP-synth ase can be demonstrated in fibroblasts exposed to 4 mmol/l calcium (12 7% of control). Mitochondrial recovery was unchanged under the differe nt incubation conditions as judged by the activity of mitochondrial ma rker enzymes. We conclude that direct regulation at the level of ATP-s ynthase occurs in vivo in human fibroblasts, The naturally occurring i nhibitor protein IF1 and the calcium binding inhibitor protein CaBI ma y be involved in this regulation of ATP-synthase.