Abstract
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.
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Abbreviations
- Δp :
-
Protonmotive force
- IMM:
-
Inner mitochondrial membrane
- MILS:
-
Maternally inherited Leigh syndrome
- MLASA:
-
Myopathy, lactic acidosis, and sideroblastic anemia
- NARP:
-
Neuropathy, ataxia, and retinitis pigmentosa
- PTP:
-
Permeability transition pore
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Trombetti, F., Pagliarani, A., Ventrella, V. et al. Crucial aminoacids in the FO sector of the F1FO-ATP synthase address H+ across the inner mitochondrial membrane: molecular implications in mitochondrial dysfunctions. Amino Acids 51, 579–587 (2019). https://doi.org/10.1007/s00726-019-02710-9
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DOI: https://doi.org/10.1007/s00726-019-02710-9