Physiological effectors modify voltage sensing by the cyclosporin A-sensitive permeability transition pore of mitochondria.

摘要: Abstract This paper reports an investigation on the modulation of mitochondrial permeability transition pore (MTP) by membrane potential. Energized rat liver mitochondria loaded with a small Ca2+ pulse in sucrose medium supplemented phosphate favor high MTP "closed" probability because potential and therefore maintain low to sucrose. Upon depolarization addition fully uncoupling concentrations carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) "open" rapidly undergo process osmotic swelling following diffusion toward matrix. A titration FCCP reveals that discrete subpopulations different gating potentials for opening may exist, since increasing increase fraction undergoing swelling. We show physiological effectors (Ca2+, Mg2+, ADP, palmitate) modify population shifting functionally open at any given Many inducers inhibitors affect directly through effect voltage sensing rather than indirectly Thus, many induce higher levels, whereas closure lower levels.