title: Dynamic changes in the subcellular distribution of Gpd1p in response to cell stress.
abstract: Gpd1p is a cytosolic NAD(+)-dependent glycerol 3-phosphate dehydrogenase that also localizes to peroxisomes and plays an essential role in the cellular response to osmotic stress and a role in redox balance. Here, we show that Gpd1p is directed to peroxisomes by virtue of an N-terminal type 2 peroxisomal targeting signal (PTS2) in a Pex7p-dependent manner. Significantly, localization of Gpd1p to peroxisomes is dependent on the metabolic status of cells and the phosphorylation of aminoacyl residues adjacent to the targeting signal. Exposure of cells to osmotic stress induces changes in the subcellular distribution of Gpd1p to the cytosol and nucleus. This behavior is similar to Pnc1p, which is coordinately expressed with Gpd1p, and under conditions of cell stress changes its subcellular distribution from peroxisomes to the nucleus where it mediates chromatin silencing. Although peroxisomes are necessary for the beta-oxidation of fatty acids in yeast, the localization of Gpd1p to peroxisomes is not. Rather, shifts in the distribution of Gpd1p to different cellular compartments in response to changing cellular status suggests a role for Gpd1p in the spatial regulation of redox potential, a process critical to cell survival, especially under the complex stress conditions expected to occur in the wild.
authors.affiliation: Institute for Systems Biology, Seattle, Washington 98103, USA.
authors.forename: Sunhee
authors.initials: S
authors.lastname: Jung
authors.forename: Marcello
authors.initials: M
authors.lastname: Marelli
authors.forename: Richard A
authors.initials: RA
authors.lastname: Rachubinski
authors.forename: David R
authors.initials: DR
authors.lastname: Goodlett
authors.forename: John D
authors.initials: JD
authors.lastname: Aitchison
mesh_terms: D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D000074437:Peroxisomal Targeting Signal 2 Receptor; D020675:Peroxisomes / Q000201:enzymology / Q000378:metabolism*; D021381:Protein Transport; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D015003:Yeasts / Q000378:metabolism
chemical_list: D000074437:Peroxisomal Targeting Signal 2 Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D005993:Glycerolphosphate Dehydrogenase