Mitochondria-mediated nuclear mutator phenotype in Saccharomyces cerevisiae
AUTOR(ES)
Rasmussen, Anne Karin
FONTE
Oxford University Press
RESUMO
Using Saccharomyces cerevisiae as a model organism, we analyzed the consequences of disrupting mitochondrial function on mutagenesis of the nuclear genome. We measured the frequency of canavanine-resistant colonies as a measure of nuclear mutator phenotype. Our data suggest that mitochondrial dysfunction leads to a nuclear mutator phenotype (i) when oxidative phosphorylation is blocked in wild-type yeast at mitochondrial complex III by antimycin A and (ii) in mutant strains lacking the entire mitochondrial genome (rho0) or those with deleted mitochondrial DNA (rho–). The nuclear mutation frequencies obtained for antimycin A-treated cells as well as for rho– and rho0 cells were ∼2- to 3-fold higher compared to untreated control and wild-type cells, respectively. Blockage of oxidative phosphorylation by antimycin A treatment led to increased intracellular levels of reactive oxygen species (ROS). In contrast, inactivation of mitochondrial activity (rho– and rho0) led to decreased intracellular levels of ROS. We also demonstrate that in rho0 cells the REV1, REV3 and REV7 gene products, all implicated in error-prone translesion DNA synthesis (TLS), mediate mutagenesis in the nuclear genome. However, TLS was not involved in nuclear DNA mutagenesis caused by inhibition of mitochondrial function by antimycin A. Together, our data suggest that mitochondrial dysfunction is mutagenic and multiple pathways are involved in this nuclear mutator phenotype.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=165961Documentos Relacionados
- Lactacystin requires reactive oxygen species and Bax redistribution to induce mitochondria-mediated cell death
- Aqueous Extract of Terminalia chebula Induces Apoptosis in Lung Cancer Cells Via a Mechanism Involving Mitochondria-mediated Pathways
- Nuclear Mutations in Saccharomyces Cerevisiae That Affect the Escape of DNA from Mitochondria to the Nucleus
- Mutator Activity of Petite Strains of SACCHAROMYCES CEREVISIAE
- The proteome of Saccharomyces cerevisiae mitochondria