Predicting the contribution of novel POLG mutations to human disease through analysis in yeast model

Enrico Baruffini; Rita Horvath; Cristina Dallabona; Birgit Czermin; Eleonora Lamantea; Laurence Bindoff; Federica Invernizzi; Iliana Ferrero; Massimo Zeviani; Tiziana Lodi

doi:10.1016/j.mito.2010.09.007

Predicting the contribution of novel POLG mutations to human disease through analysis in yeast model

Enrico Baruffini, Rita Horvath, Cristina Dallabona, Birgit Czermin, Eleonora Lamantea, Laurence Bindoff, Federica Invernizzi, Iliana Ferrero, Massimo Zeviani, Tiziana Lodi

Fondazione IRCCS Istituto Neurologico "C. Besta"

Research output: Contribution to journal › Article

Abstract

The yeast Saccharomyces cerevisiae was used to validate the pathogenic significance of eight human mutations in the gene encoding for the mitochondrial DNA polymerase gamma, namely G303R, S305R, R386H, R574W, P625R, D930N, K947R and P1073L, among which three are novel and four are of unclear pathological significance. Mitochondrial DNA extended and point mutability as well as dominance/recessivity of each mutation has been evaluated. The analysis in yeast revealed that two mutations, S305R and R386H, cannot be the sole cause of pathology observed in patients. These data led us to search for a second mutation in compound with S305R and we found a mutation, P1073L, missed in the first genetic analysis. Finally, a significant rescue of extended mutability has been observed for several dominant mutations by treatment with mitochondrial antioxidants.

Original language	English
Pages (from-to)	182-190
Number of pages	9
Journal	Mitochondrion
Volume	11
Issue number	1
DOIs	https://doi.org/10.1016/j.mito.2010.09.007
Publication status	Published - Jan 2011

Keywords

MIP1
Mitochondrial diseases
MtDNA mutability
POLG
ROS scavengers
Yeast model

ASJC Scopus subject areas

Cell Biology
Molecular Biology
Molecular Medicine

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Baruffini, E., Horvath, R., Dallabona, C., Czermin, B., Lamantea, E., Bindoff, L., Invernizzi, F., Ferrero, I., Zeviani, M., & Lodi, T. (2011). Predicting the contribution of novel POLG mutations to human disease through analysis in yeast model. Mitochondrion, 11(1), 182-190. https://doi.org/10.1016/j.mito.2010.09.007

Predicting the contribution of novel POLG mutations to human disease through analysis in yeast model. / Baruffini, Enrico; Horvath, Rita; Dallabona, Cristina; Czermin, Birgit; Lamantea, Eleonora; Bindoff, Laurence; Invernizzi, Federica; Ferrero, Iliana; Zeviani, Massimo; Lodi, Tiziana.

In: Mitochondrion, Vol. 11, No. 1, 01.2011, p. 182-190.

Research output: Contribution to journal › Article

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