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, 25734-257401, 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.
Martinucci
S
S
Centro CNR Biomembrane e Dipartimento di Scienze Biomediche, Università di Padova, Padua, Italy.
Szabò
I
I
Tombola
F
F
Zoratti
M
M
D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002413:Cations, Divalent; D007473:Ion Channels; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000502:physiology*; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D051381:Rats; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
D016227:Benzoquinones; D002413:Cations, Divalent; D007473:Ion Channels; D008565:Membrane Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D014451:Ubiquinone; C060262:2,3-dimethoxy-5-methyl-6-decyl-1,4-benzoquinone; C109863:ubiquinone-O; C003741:ubiquinol; D002118:Calcium