title: Preferential nitrite inhibition of the mitochondrial F1FO-ATPase activities when activated by Ca(2+) in replacement of the natural cofactor Mg(2+).
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 Ca(2+), henceforth defined as Ca-ATPase(s), or by the natural cofactor Mg(2+), was investigated by evaluating ATP hydrolysis under different assay conditions.
  
  
  RESULTS
  Ca(2+) is far less efficient than the natural cofactor Mg(2+) in the ATPase activation. However, when activated by Ca(2+) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Veterinary Medical Sciences (DIMEVET), University of Bologna, Via Tolara di Sopra 50, 40064 Ozzano Emilia (BO), Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Nesci
authors.affiliation: Department of Veterinary Medical Sciences (DIMEVET), University of Bologna, Via Tolara di Sopra 50, 40064 Ozzano Emilia (BO), Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Ventrella
authors.affiliation: Department of Veterinary Medical Sciences (DIMEVET), University of Bologna, Via Tolara di Sopra 50, 40064 Ozzano Emilia (BO), Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Trombetti
authors.affiliation: Department of Veterinary Medical Sciences (DIMEVET), University of Bologna, Via Tolara di Sopra 50, 40064 Ozzano Emilia (BO), Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pirini
authors.affiliation: Department of Veterinary Medical Sciences (DIMEVET), University of Bologna, Via Tolara di Sopra 50, 40064 Ozzano Emilia (BO), Italy. Electronic address: alessandra.pagliarani@unibo.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pagliarani
mesh_terms: D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000037:antagonists & inhibitors; D002118:Calcium / Q000494:pharmacology*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D008274:Magnesium / Q000494:pharmacology; D025261:Mitochondrial Proton-Translocating ATPases / Q000037:antagonists & inhibitors*; D009573:Nitrites / Q000494:pharmacology*; D013552:Swine
chemical_list: D009573:Nitrites; D017301:Ca(2+) Mg(2+)-ATPase; D025261:Mitochondrial Proton-Translocating ATPases; D000252:Calcium-Transporting ATPases; D008274:Magnesium; D002118:Calcium
keywords: Calcium; Dityrosine; F(1)F(O)-ATPase; Mitochondria; Nitrite; Post-translational modifications