1. The mitochondrial F 1 F O -ATPase exploits the dithiol redox state to modulate the permeability transition pore.
- Author
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Algieri C, Trombetti F, Pagliarani A, Ventrella V, and Nesci S
- Subjects
- Animals, Arsenicals pharmacology, Bridged Bicyclo Compounds pharmacology, Calcium metabolism, Dithioerythritol pharmacology, Enzyme Activators pharmacology, Enzyme Inhibitors pharmacology, Magnesium metabolism, Mitochondria drug effects, Oxidation-Reduction drug effects, Oxidative Stress drug effects, Proton-Translocating ATPases antagonists & inhibitors, Proton-Translocating ATPases chemistry, Swine, Cysteine chemistry, Mitochondrial Permeability Transition Pore metabolism, Proton-Translocating ATPases metabolism
- Abstract
The dithiol reagents phenylarsine oxide (PAO) and dibromobimane (DBrB) have opposite effects on the F
1 FO -ATPase activity. PAO 20% increases ATP hydrolysis at 50 μM when the enzyme activity is activated by the natural cofactor Mg2+ and at 150 μM when it is activated by Ca2+ . The PAO-driven F1 FO -ATPase activation is reverted to the basal activity by 50 μM dithiothreitol (DTE). Conversely, 300 μM DBrB decreases the F1 FO -ATPase activity by 25% when activated by Mg2+ and by 50% when activated by Ca2+ . In both cases, the F1 FO -ATPase inhibition by DBrB is insensitive to DTE. The mitochondrial permeability transition pore (mPTP) formation, related to the Ca2+ -dependent F1 FO -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 F1 FO -ATPase, with (ir)reversible redox states, in the mPTP modulation., (Copyright © 2021 Elsevier Inc. All rights reserved.)- Published
- 2021
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