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Yeast Pah1p phosphatidate phosphatase is subject to proteasome‐mediated degradation
Author(s) -
Pascual Florencia,
SotoCardalda Anibal,
Carman George M.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.822.8
Subject(s) - phosphatidate , diacylglycerol kinase , biochemistry , phosphatase , microbiology and biotechnology , vacuole , chemistry , biology , enzyme , cytoplasm , protein kinase c
In yeast, Pah1p phosphatidate (PA) phosphatase catalyzes the penultimate step in the synthesis of triacylglycerol. The importance of this enzyme is exemplified by the severe phenotypes of the pah1 Δ mutant that include deregulation of phospholipid synthesis, an aberrant expansion of the nuclear/ER membrane, a decrease in lipid droplet formation, a massive reduction in triacylglycerol content, defects in vacuole homeostasis and fusion, and increased sensitivity to lipotoxicity. On the other hand, the attenuation of Pah1p PA phosphatase function is also essential to normal cell physiology. Indeed, the overexpression of an unregulated form of PA phosphatase inhibits cell growth, and this is attributed to the depletion of PA needed for phospholipid synthesis via CDP‐diacylglycerol and the accumulation of diacylglycerol to a toxic level. Triacylglycerol accumulates in the stationary phase of growth, and the lipid analysis of the pah1 Δ mutant established the essential role of Pah1p PA phosphatase in this process. While the PA phosphatase activity was elevated in stationary phase cells, the expression of PAH1 mRNA and Pah1p was maximal in the exponential phase, but declined as cells entered the stationary phase. The levels of Pah1p were stabilized in stationary phase cells treated with the proteasome inhibitor MG132 as well as in several mutants that exhibit a decrease in proteasome function. This work reveals a novel mechanism for the control of Pah1p PA phosphatase function in yeast. Supported by NIH grant GM 28140.