The mitochondrial F1FO-ATPase revealed double-faced roles: its main role of producing ATP seems to counteract the ability to cause cell death. Indeed, under conditions of Ca+2 accumulation, the F1FO-ATPase triggers the so-called Mitochondrial Permeability Transition (MPT) a lethal cellular event. Accordingly, F1FO-ATPase dymers would generate similar Ca+2-dependent currents to MPT pore ones [1]. The F1FO-ATPase is more effectively inhibited by nitrite (NO2-) when activated by Ca2+ than by the natural cofactor Mg+2. In the presence of Ca+2 or Mg+2, NO2- uncompetitively inhibits the enzyme with respect to ATP substrate and inhibition extent depends on the cation. While NO2- inhibition is not prevented by ascorbate, ruling out any S-nitrosylation, it is enhanced by hydrogen peroxide (H2O2). The H2O2–driven production of nitrogen dioxide radical (•NO2) could cause post-translational modifications of tyrosine residues in the catalytic F1 sector. Since NO2-, especially provided by Mediterranean diets, acts as a vascular endocrine nitric oxide reservoir, it may protect against MPT events under ischemia/reperfusion conditions. 1. Antoniel M. et al. 2014. Int J Mol Sci 15:7513-36.
Salvatore Nesci, Vittoria Ventrella, Fabiana Trombetti, Alessandra Pagliarani (2014). Modulation of mitochondrial Ca+2 and Mg+2 dependent F1FO-ATPase by nitrite.
Modulation of mitochondrial Ca+2 and Mg+2 dependent F1FO-ATPase by nitrite
NESCI, SALVATORE;VENTRELLA, VITTORIA;TROMBETTI, FABIANA;PAGLIARANI, ALESSANDRA
2014
Abstract
The mitochondrial F1FO-ATPase revealed double-faced roles: its main role of producing ATP seems to counteract the ability to cause cell death. Indeed, under conditions of Ca+2 accumulation, the F1FO-ATPase triggers the so-called Mitochondrial Permeability Transition (MPT) a lethal cellular event. Accordingly, F1FO-ATPase dymers would generate similar Ca+2-dependent currents to MPT pore ones [1]. The F1FO-ATPase is more effectively inhibited by nitrite (NO2-) when activated by Ca2+ than by the natural cofactor Mg+2. In the presence of Ca+2 or Mg+2, NO2- uncompetitively inhibits the enzyme with respect to ATP substrate and inhibition extent depends on the cation. While NO2- inhibition is not prevented by ascorbate, ruling out any S-nitrosylation, it is enhanced by hydrogen peroxide (H2O2). The H2O2–driven production of nitrogen dioxide radical (•NO2) could cause post-translational modifications of tyrosine residues in the catalytic F1 sector. Since NO2-, especially provided by Mediterranean diets, acts as a vascular endocrine nitric oxide reservoir, it may protect against MPT events under ischemia/reperfusion conditions. 1. Antoniel M. et al. 2014. Int J Mol Sci 15:7513-36.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
