The mitochondrial F1FO-ATPase exploits the dithiol redox state to modulate the permeability transition pore

The dithiol reagents phenylarsine oxide (PAO) and dibromobimane (DBrB) have opposite effects on the F1FO-ATPase activity. PAO 20% increases ATP hydrolysis at 50 mu M when the enzyme activity is activated by the natural cofactor Mg2+ and at 150 mu M when it is activated by Ca2+. The PAO-driven F1FO-ATPase activation is reverted to the basal activity by 50 mu M dithiothreitol (DTE). Conversely, 300 mu M DBrB decreases the F1FO-ATPase activity by 25% when activated by Mg2+ and by 50% when activated by Ca2+. In both cases, the F1FO-ATPase inhibition by DBrB is insensitive to DTE. The mitochondrial permeability transition pore (mPTP) formation, related to the Ca2+-dependent F1FO-ATPase activity, is stimulated by PAO and desensitized by DBrB. Since PAO and DBrB apparently form adducts with different cysteine couples, the results highlight the crucial role of cross linking of vicinal dithiols on the F1FO-ATPase, with (ir)reversible redox states, in the mPTP modulation.

Automated summary

The dithiol reagents phenylarsine oxide (PAO) and dibromobimane (DBrB) have opposite effects on the F1FO-ATPase activity, with PAO increasing the activity and DBrB decreasing it. Additionally, PAO stimulates the formation of the mitochondrial permeability transition pore (mPTP) while DBrB desensitizes it.