Nesci 2016 Biochim Biophys Acta
| Nesci S, Ventrella V, Trombetti F, Pirini M, Pagliarani A (2016) Preferential nitrite inhibition of the mitochondrial F1FO-ATPase activities when activated by Ca(2+) in replacement of the natural cofactor Mg(2.). Biochim Biophys Acta 1860:345-53. |
Nesci S, Ventrella V, Trombetti F, Pirini M, Pagliarani A (2016) Biochim Biophys Acta
Abstract: Background The mitochondrial F1FO-ATP synthase has not only the known life function in building most cellular ATP, but also, as recently hinted, an amazing involvement in cell death. Accordingly, the two-faced enzyme complex, which catalyzes both ATP synthesis and ATP hydrolysis, has been involved in the mitochondrial permeability transition, the master player in apoptosis and necrosis. Nitrite, a cellular nitric oxide reservoir, has a recognized role in cardiovascular protection, through still unclear mechanisms.
Methods In swine heart mitochondria the effect of nitrite on the F1FO-ATPase activity activated by Ca2+, henceforth defined as Ca-ATPase(s), or by the natural cofactor Mg2+, was investigated by evaluating ATP hydrolysis under different assay conditions.
Results Ca2+ is far less efficient than the natural cofactor Mg2+ in the ATPase activation. However, when activated by Ca2+ the ATPase activity is especially responsive to nitrite, which acts as uncompetitive inhibitor and up to 2 mM inhibits the Ca2+-activated-ATPase(s), probably by promoting dytirosine formation on the enzyme proteins, leaving the Mg-ATPase(s) unaffected. Most likely these ATPases refer to the same F1FO complex, even if coexistent ATPases may overlap.
Conclusions The preferential inhibition by nitrite of the Ca-ATPase(s), due to post-translational tyrosine modifications, may prevent the calcium-dependent functionality of the mitochondrial F1FO complex and related events.
General significance In mitochondria the preferential inhibition of the Ca-ATPase activity/ies by nitrite concentrations which do not affect the coexistent Mg-ATPase(s) may quench the negative events linked to the calcium-dependent functioning mode of the F1FO complex under pathological conditions. • Keywords: Calcium, Dityrosine, F(1)F(O)-ATPase, Mitochondria, Nitrite, Post-translational modifications
Labels:
Stress:Cell death, Permeability transition Organism: Pig
Regulation: ATP production
