Altered metabolic regulation owing to gsp1 mutations encoding the nuclear small G protein in Saccharomyces cerevisiae.

Abstract

Nutrient metabolism is regulated for adaptation to, for example, environmental alterations, cellular stress, cell cycle, and cellular ageing. This regulatory network consists of cross-talk between cytoplasmic organelles and the nucleus. The ras-like nuclear small G protein, Ran, functions in nuclear-cytosolic transport and regulatory signal transmission. In yeast, some genes involved in the Ran system in yeast are required for growth on glycerol medium. Growth deficiency, due to mutations in the GSP1 gene, which encodes Ran, is allele specific. Specifically in this study, the gsp1-1894 cells lost mitochondria, and could not grow on media containing glycerol, galactose or maltose. However, the gsp1-1894 cells grew better on a high salt medium (1M NaCl) and had increased expression levels of GPD1-lacZ. Furthermore, disruption of the HOG1 gene suppressed their growth deficiency on glycerol medium. These findings suggest that altered activation of Hog1 in the gsp1-1894 cells resulted in the loss of mitochondria and inhibition of glycerol metabolism. Growth deficiency of the gsp1-1894 cells on galactose medium was further suppressed by high dosage of the SIP2 DNA, which encodes the cytosolic β subunit of AMPK. This suggests that higher cytosolic activity of AMPK is required for the utilization of an alternative carbon source in gsp1-1894 cells.