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

Ubiquinone 0 and decylubiquinone have been reported to inhibit the mitochon drial permeability transition pore (PTP) [Fontaine, E,, Ichas, F, and Berna rdi, P, (1998) J, Biol. Chem, 273, 25734-25740], offering a new clue to its molecular composition. In patch-clamp experiments on rat liver mitochondri a we have observed that these compounds also inhibit the previously describ ed mitochondrial megachannel (MMC), confirming its identification as the PT P. Inhibition can be reversed by increasing [Ca2+], in analogy to the behav ior observed,vith several other disparate PTP/MMC inhibitors, To rationaliz e the ability of Ca2+ to overcame inhibition by various quite different com pounds we propose that it acts via the phospholipid bilayer. (C) 2000 Feder ation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.