Amino Acids

, Volume 51, Issue 4, pp 579–587 | Cite as

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

  • Fabiana Trombetti
  • Alessandra PagliaraniEmail author
  • Vittoria Ventrella
  • Cristina Algieri
  • Salvatore Nesci
Minireview Article


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.


Crucial aminoacids a Subunit F1FO-ATP synthase H+ pathway Mitochondrial dysfunctions 



Protonmotive force


Inner mitochondrial membrane


Maternally inherited Leigh syndrome


Myopathy, lactic acidosis, and sideroblastic anemia


Neuropathy, ataxia, and retinitis pigmentosa


Permeability transition pore



Funding was provided by the University of Bologna, Italy.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

The manuscript complies with the ethical rules applicable for the journal and the research does not involve data regarding humans or animals.


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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Veterinary Medical SciencesUniversity of BolognaOzzano EmiliaItaly

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