Yeast models of mutations in the mitochondrial ATP6 gene found in human cancer cells

Mitochondrion. 2016 Jul:29:7-17. doi: 10.1016/j.mito.2016.04.003. Epub 2016 Apr 12.


Since the discovery of somatic mtDNA mutations in tumor cells, multiple studies have focused on establishing a causal relationship between those changes and alterations in energy metabolism, a hallmark of cancer cells. Yet the consequences of these mutations on mitochondrial function remain largely unknown. In this study, Saccharomyces cerevisiae has been used as a model to investigate the functional consequences of four cancer-associated missense mutations (8914C>A, 8932C>T, 8953A>G, 9131T>C) found in the mitochondrial MT-ATP6 gene. This gene encodes the a-subunit of F1FO-ATP synthase, which catalyzes the last steps of ATP production in mitochondria. Although the four studied mutations affected well-conserved residues of the a-subunit, only one of them (8932C>T) had a significant impact on mitochondrial function, due to a less efficient incorporation of the a-subunit into ATP synthase. Our findings indicate that these ATP6 genetic variants found in human tumors are neutral mitochondrial genome substitutions with a limited, if any, impact on the energetic function of mitochondria.

Keywords: ATP synthase; Bioenergetics; Cancer; MT-ATP6; Mitochondria; mtDNA mutation.

MeSH terms

  • Humans
  • Mitochondrial Proton-Translocating ATPases / genetics*
  • Mitochondrial Proton-Translocating ATPases / metabolism*
  • Models, Biological*
  • Mutagenesis, Site-Directed
  • Mutation, Missense*
  • Neoplasms / pathology
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism*


  • ATP6 protein, S cerevisiae
  • MT-ATP6 protein, human
  • Saccharomyces cerevisiae Proteins
  • Mitochondrial Proton-Translocating ATPases