Mini-review. Nitrite as novel pore-shutter: hints from the preferential inhibition of the mitochondrial ATP-ase when activated by Ca2+

Small inorganic compounds able to prevent the mitochondrial permeability transition, the master player in apoptosis and necrosis, are increasingly considered as beneficial tools in cytoprotection. Nitrite, a known cellular nitric oxide reservoir, has a recognized role in cardioprotection, but the molecular mechanisms of its action are not thoroughly understood. Mitochondrial permeability changes are known to constitute the molecular bases of human cardiac diseases and pathologies related to mitochondrial dysfunctions. In turn oxidative stress and mitochondrial damage are related issues in degenerative and cardiovascular diseases. Assumed that the mitochondrial F1FO complex is structurally or functionally involved in the mitochondrial permeability transition pore (MPTP), which triggers the mitochondrial permeability transition, nitrite effects on the enzyme complex may be exploited to shut the MPTP. Many clues suggest that nitrite may prevent or limit cell death by modulating the F1FO complex. Accordingly, nitrite decreases the ATPase activity stimulated by Ca2+, it is ineffective on the Mg-ATPase up to 2 mM and the enzyme inhibition is apparently enhanced under oxidative stress conditions. Through the inhibition of the calcium-activated F1FO complex, nitrite would shut the MPTP, which is likely to be related to the calcium-dependent functioning mode of the F1FO complex, and limit mitochondrial impairment and cell death under physio-pathological conditions.