The mitochondrial effects of two fluoride curcumin derivatives were studied. They induced the collapse of mitochondrial membrane potential (DeltaPsi), increased mitochondrial respiration, and decreased O(2)*- production and promoted Ca(2+) release. These effects were reversed by the recoupling agent 6-Ketocholestanol, but not by cyclosporin A, an inhibitor of the permeability transition pore (PTP), suggesting that these compounds act as uncoupling agents. This idea was reinforced by the analysis of the physico-chemical properties of the compounds indicating, that they are mainly in the anionic form in the mitochondrial membrane. Moreover, they are able to induce PTP opening by promoting the oxidation of thiol groups and the release of cytochrome c, making these two molecules potential candidates for induction of apoptosis.