Inhibition of the mitochondrial cyclosporin A-sensitive permeability transition pore by the arginine reagent phenylglyoxal.

The mitochondrial permeability transition pore, a cyclosporin A-sensitive channel, is controlled by the transmembrane electric potential difference across the inner membrane. Here, we show that treatment of rat liver mitochondria with the arginine reagent phenylglyoxal inhibits the permeability transition pore triggered by depolarization with uncoupler after Ca2+ accumulation. Phenylglyoxal does not change the extent of mitochondrial Ca2+ uptake or the extent of membrane depolarization, indicating that covalent modification of arginine (and possibly lysine) residues directly affects the open probability of the pore. We propose that arginine residues play a role in the physiological control of the permeability transition pore by the mitochondrial transmembrane potential.