Selective inhibition of the mitochondrial permeability transition pore at the oxidation-reduction sensitive dithiol by monobromobimane

FEBS Lett. 1995 Apr 3;362(2):239-42. doi: 10.1016/0014-5793(95)00256-9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Bridged Bicyclo Compounds / pharmacology*
  • Calcium / metabolism
  • Calcium Channels / metabolism
  • Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / pharmacology
  • Cyclosporine / pharmacology
  • Intracellular Membranes / drug effects
  • Ion Channel Gating / drug effects
  • Ion Channels / antagonists & inhibitors*
  • Mitochondria, Liver / drug effects*
  • Mitochondria, Liver / metabolism
  • Oxidation-Reduction
  • Oxygen Consumption / drug effects
  • Permeability / drug effects
  • Phosphates / metabolism
  • Rats
  • Toluene / analogs & derivatives*
  • Toluene / antagonists & inhibitors

Substances

  • Bridged Bicyclo Compounds
  • Calcium Channels
  • Ion Channels
  • Phosphates
  • Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
  • Toluene
  • Cyclosporine
  • Adenosine Triphosphate
  • Calcium
  • dithiol
  • monobromobimane