Abstract
In the yeast Saccharomyces cerevisiae, the synthesis of phospholipids is coordinately regulated by mechanisms that control the homeostasis of the essential mineral zinc (Carman, G.M., and Han, G. S. (2007) Regulation of phospholipid synthesis in Saccharomyces cerevisiae by zinc depletion. Biochim. Biophys. Acta 1771, 322-330; Eide, D. J. (2009) Homeostatic and adaptive responses to zinc deficiency in Saccharomyces cerevisiae. J. Biol. Chem. 284, 18565-18569). The synthesis of phosphatidylcholine is balanced by the repression of CDP-diacylglycerol pathway enzymes and the induction of Kennedy pathway enzymes. PAH1-encoded phosphatidate phosphatase catalyzes the penultimate step in triacylglycerol synthesis, and the diacylglycerol generated in the reaction may also be used for phosphatidylcholine synthesis via the Kennedy pathway. In this work, we showed that the expression of PAH1-encoded phosphatidate phosphatase was induced by zinc deficiency through a mechanism that involved interaction of the Zap1p zinc-responsive transcription factor with putative upstream activating sequence zinc-responsive elements in the PAH1 promoter. The pah1Δ mutation resulted in the derepression of the CHO1-encoded phosphatidylserine synthase (CDP-diacylglycerol pathway enzyme) and loss of the zinc-mediated regulation of the enzyme. Loss of phosphatidate phosphatase also resulted in the derepression of the CKI1-encoded choline kinase (Kennedy pathway enzyme) but decreased the synthesis of phosphatidylcholine when cells were deficient of zinc. This result confirmed the role phosphatidate phosphatase plays in phosphatidylcholine synthesis via the Kennedy pathway.
Highlights
In yeast, phospholipid synthesis is regulated by zinc deficiency
Zinc Deficiency Causes Zap1p-dependent Induction of PA Phosphatase Activity—We addressed the hypothesis that PAH1-encoded PA phosphatase was regulated by zinc deficiency
We examined the effect of zinc deficiency on PA phosphatase activity in dpp1⌬ lpp1⌬ mutant cells that lack both Dpp1p and Lpp1p (Fig. 2A)
Summary
Phospholipid synthesis is regulated by zinc deficiency. Results: PAH1-encoded phosphatidate phosphatase activity was induced in zinc-deficient cells by a transcriptional mechanism. Loss of phosphatidate phosphatase resulted in the derepression of the CKI1-encoded choline kinase (Kennedy pathway enzyme) but decreased the synthesis of phosphatidylcholine when cells were deficient of zinc. A reduction in the content of PA (which tethers Opi1p and stabilizes its association with Scs2p at the nuclear/ER membrane [9, 12]), which is caused by the increased synthesis of PI via CDP-DAG, leads to the translocation of Opi1p into the nucleus where it interacts with Ino2p to attenuate the transcriptional activation of CHO1 by the Ino2p-Ino4p complex [9, 13,14,15] This regulation occurs in the absence of inositol supplementation, a growth condition that represses the expression of CHO1 and other UASINO-containing phospholipid synthesis genes [4, 15,16,17]. Be identified, was induced in response to zinc depletion through a mechanism that involved Zap1p
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