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.
The mitochondrial F1FO-ATPase exploits the dithiol redox state to modulate the permeability transition pore / Algieri, Cristina; Trombetti, Fabiana; Pagliarani, Alessandra; Ventrella, Vittoria; Nesci, Salvatore. - In: ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS. - ISSN 0003-9861. - STAMPA. - 712:(2021), pp. 109027.1-109027.5. [10.1016/j.abb.2021.109027]
The mitochondrial F1FO-ATPase exploits the dithiol redox state to modulate the permeability transition pore
Algieri, CristinaPrimo
;Trombetti, Fabiana;Pagliarani, Alessandra;Ventrella, Vittoria;Nesci, Salvatore
Ultimo
Supervision
2021
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.File | Dimensione | Formato | |
---|---|---|---|
postprint_YABBI_109027.pdf
Open Access dal 13/09/2022
Tipo:
Postprint
Licenza:
Licenza per Accesso Aperto. Creative Commons Attribuzione - Non commerciale - Non opere derivate (CCBYNCND)
Dimensione
1.36 MB
Formato
Adobe PDF
|
1.36 MB | Adobe PDF | Visualizza/Apri |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.