Selective inhibition of the mitochondrial permeability transition pore at the oxidation-reduction sensitive dithiol by monobromobimane.
In this paper we introduce monobromobimane, a thiol reagent, as a selective blocker of the recently identified dithiol whose oxidation-reduction status modifies voltage sensing by the mitochondrial permeability transition pore, a cyclosporin A-sensitive channel. Monobromobimane does not inhibit the phosphate carrier, nor does it interfere with Ca2+ transport, energy coupling or ATP production and transport. We show that monobromobimane selectively prevents the shift in pore gating potential caused by some dithiol oxidants or crosslinkers but not by increasing [Ca2+], allowing a clear distinction of the pore agonists which act at this site.
Costantini
P
P
CNR Unit for the Study of Physiology of Mitochondria, University of Padova Medical School, Italy.
Chernyak
B V
BV
Petronilli
V
V
Bernardi
P
P
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D007425:Intracellular Membranes / Q000187:drug effects; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000037:antagonists & inhibitors*; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D014050:Toluene / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors
D001643:Bridged Bicyclo Compounds; D015220:Calcium Channels; D007473:Ion Channels; D010710:Phosphates; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D014050:Toluene; D016572:Cyclosporine; D000255:Adenosine Triphosphate; D002118:Calcium; C004848:dithiol; C028381:monobromobimane