Fibrillarin (FBL) is an essential nucleolar protein that participates in pre-rRNA methylation and processing. The methyltransferase domain of FBL is an example of an extremely well-conserved protein domain in which the amino acid sequence was not substantially modified during the evolution fromArchaeatoEukaryota. An additional N-terminal glycine–arginine-rich (GAR) domain is present in the FBL of eukaryotes. Here, we demonstrate that the GAR domain is involved in FBL functioning and integrates the functions of the nuclear localization signal and the nucleolar localization signal (NoLS). The methylation of the arginine residues in the GAR domain is necessary for nuclear import but decreases the efficiency of nucleolar retention via the NoLS. The presented data indicate that the GAR domain can be considered an evolutionary innovation that integrates several functional activities and thereby adapts FBL to the highly compartmentalized content of the eukaryotic cell.

Sterols are important components of biological membranes that determine the physicochemical properties of lipid bilayer and regulate the functioning of membrane proteins. Being insoluble in water,...

Non-identical copies of mitochondrial DNA (mtDNA) compete with each other within a cell and the ultimate variant of mtDNA present depends on their relative replication rates. Using yeast Saccharomyces cerevisiae cells as a model, we studied the effects of mitochondrial inhibitors on the competition between wild-type mtDNA and mutant selfish mtDNA in heteroplasmic zygotes. We found that decreasing mitochondrial transmembrane potential by adding uncouplers or valinomycin changes the competition outcomes in favor of the wild-type mtDNA. This effect was significantly lower in cells with disrupted mitochondria fission or repression of the autophagy-related genes ATG8, ATG32 or ATG33, implying that heteroplasmic zygotes activate mitochondrial degradation in response to the depolarization. Moreover, the rate of mitochondrially targeted GFP turnover was higher in zygotes treated with uncoupler than in haploid cells or untreated zygotes. Finally, we showed that vacuoles of zygotes with uncoupler-activated autophagy contained DNA. Taken together, our data demonstrate that mitochondrial depolarization inhibits clonal expansion of selfish mtDNA and this effect depends on mitochondrial fission and autophagy. These observations suggest an activation of mitochondria quality control mechanisms in heteroplasmic yeast zygotes.

How do yeast sense mitochondrial dysfunction? –

The budding yeast Saccharomyces cerevisiae actively transports adverse factors (e.g. oxidized proteins) from the daughter to mother cells. The transport is believed to ensure that the daughters are born "young", thus preventing clonal senescence. Is this the only reason for the existence of such transport? We subjected yeast cells to various stress conditions and compared survival of mother and daughter cells. It was found that replicative age-dependent mortality under our experimental stress conditions was U-shaped: the resistance of both virgin daughters and old mother cells (more than three bud scars) was lower compared to the young mothers. SIR2 mutants were shown to fail to maintain the mother-daughter asymmetry. We showed that sir2 knockout affects the relative stress resistance in favor of the mothers. Thus, daughter cells are more vulnerable to a variety of stresses than the young mothers, and Sir2-dependent transport of the adverse factors acts to equalize the resistance.