Cellular and functional analysis of four mutations located in the mitochondrial atpase6gene

Martha Elisa Vazquez-Memije, Teresa Rizza, Maria Chiara Meschini, Claudia Nesti, Filippo Maria Santorelli, Rosalba Carrozzo

Research output: Contribution to journalArticlepeer-review


The smallest rotary motor of living cells, F0F1-ATP synthase, couples proton flow-generated by the OXPHOS system-from the intermembrane space back to the matrix with the conversion of ADP to ATP. While all mutations affecting the multisubunit complexes of the OXPHOS system probably impact on the cell's output of ATP, only mutations in complex V can be considered to affect this output directly. So far, most oftheF0F1-ATP synthase variations have been detected in the mitochondrial ATPase6 gene. In this study, the four most frequent mutations in the ATPase6 gene, namely L156R, L217R, L156P, and L217P, are studied for the first time together, both in primary cells and in cybrid clones. Arginine ("R") mutations were associated with a much more severe phenotype than Proline ("P") mutations, in terms of both biochemical activity and growth capacity. Also, a threshold effect in both "R" mutations appeared at 50% mutation load. Different mechanisms seemed to emerge for the two "R" mutations: the F1 seemed loosely bound to the membrane in the L156R mutant, whereas the L217R mutant induced low activity of complex V, possibly the result of a reduced rate of proton flow through the A6 channel. J. Cell. Biochem. 106: 878-886, 2009.

Original languageEnglish
Pages (from-to)878-886
Number of pages9
JournalJournal of Cellular Biochemistry
Issue number5
Publication statusPublished - Apr 1 2009


  • ATPase6 mutations
  • F1F0-ATPase
  • Leigh syndrome
  • Mitochondria
  • OS-ATPase

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology


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