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

• 影响指数: 4.114
• 发表时间: 11 2021 15
• 来源期刊: Arch Biochem Biophys
• DOI: 10.1016/j.abb.2021.109027
• PMID: 34520732
• 文章类型: Journal Article
• 中科院分区: Q2
• 方向: 生物
• 作者列表: Algieri C,Trombetti F,Pagliarani A,Ventrella V,Nesci S

关键词: F(1)F(O)-ATPase; Mitochondria; Post-translational modification; Thiols; mPTP

Mesh: Animals; Arsenicals / pharmacology; Bridged Bicyclo Compounds / pharmacology; Calcium / metabolism; Cysteine / chemistry; Dithioerythritol / pharmacology; Enzyme Activators / pharmacology; Enzyme Inhibitors / pharmacology; Magnesium / metabolism; Mitochondria / drug effects; Mitochondrial Permeability Transition Pore / metabolism; Oxidation-Reduction / drug effects; Oxidative Stress / drug effects; Proton-Translocating ATPases / antagonists & inhibitors chemistry metabolism; Swine

Abstract

The dithiol reagents phenylarsine oxide (PAO) and dibromobimane (DBrB) have opposite effects on the F1FO-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 F1FO-ATPase activation is reverted to the basal activity by 50 μM dithiothreitol (DTE). Conversely, 300 μM 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.