Yeast models of mutations in the mitochondrial ATP6 gene found in human cancer cells
Mitochondrion. 2016-07-01; 29: 7-17
DOI: 10.1016/j.mito.2016.04.003
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1. Mitochondrion. 2016 Jul;29:7-17. doi: 10.1016/j.mito.2016.04.003. Epub 2016 Apr
12.
Yeast models of mutations in the mitochondrial ATP6 gene found in human cancer
cells.
Niedzwiecka K(1), Kabala AM(2), Lasserre JP(3), Tribouillard-Tanvier D(3), Golik
P(4), Dautant A(3), di Rago JP(3), Kucharczyk R(5).
Author information:
(1)Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw,
Poland.
(2)Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw,
Poland; Institut de Biochimie et Génétique Cellulaires, CNRS UMR5095, Université
de Bordeaux, 1 rue Camille Saint-Saëns, 33077 Bordeaux Cedex, France.
(3)Institut de Biochimie et Génétique Cellulaires, CNRS UMR5095, Université de
Bordeaux, 1 rue Camille Saint-Saëns, 33077 Bordeaux Cedex, France.
(4)Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw,
Poland; Institute of Genetics and Biotechnology, Faculty of Biology, University
of Warsaw, Poland.
(5)Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw,
Poland. Electronic address: .
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.
Copyright © 2016 Elsevier B.V. and Mitochondria Research Society. All rights
reserved.
DOI: 10.1016/j.mito.2016.04.003
PMID: 27083309 [Indexed for MEDLINE]