Ca2+-reversible inhibition of the mitochondrial megachannel by ubiquinone analogues

Ubiquinone 0 and decylubiquinone have been reported to inhibit the mitochondrial permeability transition pore (PTP) [Fontaine, E., Ichas, F. and Bernardi, P. (1998) J. Biol. Chem. 273, 25734–25740], offering a new clue to its molecular composition. In patch-clamp experiments on rat liver mitochondria we have observed that these compounds also inhibit the previously described mitochondrial megachannel (MMC), confirming its identification as the PTP. Inhibition can be reversed by increasing [Ca²⁺], in analogy to the behavior observed with several other disparate PTP/MMC inhibitors. To rationalize the ability of Ca²⁺ to overcome inhibition by various quite different compounds we propose that it acts via the phospholipid bilayer.