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Crucial aminoacids in the FO sector of the F1FO-ATP synthase address H+ across the inner mitochondrial membrane: molecular implications in mitochondrial dysfunctions

Trombetti, Fabiana, Pagliarani, Alessandra, Ventrella, Vittoria, Algieri, Cristina, Nesci, Salvatore
Amino acids 2019 v.51 no.4 pp. 579-587
H-transporting ATP synthase, adenosine triphosphate, enzyme activity, glutamic acid, hydrolysis, mitochondria, mitochondrial membrane, models, point mutation, protons
The eukaryotic F₁FO-ATP synthase/hydrolase activity is coupled to H⁺ translocation through the inner mitochondrial membrane. According to a recent model, two asymmetric H⁺ half-channels in the a subunit translate a transmembrane vertical H⁺ flux into the rotor rotation required for ATP synthesis/hydrolysis. Along the H⁺ pathway, conserved aminoacid residues, mainly glutamate, address H⁺ both in the downhill and uphill transmembrane movements to synthesize or hydrolyze ATP, respectively. Point mutations responsible for these aminoacid changes affect H⁺ transfer through the membrane and, as a cascade, result in mitochondrial dysfunctions and related pathologies. The involvement of specific aminoacid residues in driving H⁺ along their transmembrane pathway within a subunit, sustained by the literature and calculated data, leads to depict a model consistent with some mitochondrial disorders.