fig2

Figure 2. Metabolic strategies in response to low and high ATPase activity of Pgp. In the left panel drug substrates stimulate the ATPase activity of Pgp by 1.5- to 2-fold, and the energy requirements are met primarily by glycolysis. UCP2 activity reduces the extent of the PMF and ATP production by oxphos. The right panel proposes an alternative strategy in the presence of collateral sensitisers that markedly increase ATP hydrolysis. Glycolysis cannot meet the requirements of Pgp and the UCP2 control of PMF is relaxed. This enables greater mitochondrial ATP production, but this also causes increased superoxide production