Figure 3 .

Model for PA-mediated regulation of phospholipid synthesis genes. (A) Growth conditions (e.g., exponential phase, inositol depletion, or zinc supplementation) under which the levels of PA are relatively high, the Opi1 repressor is tethered to the nuclear/ER membrane, and UAS_INO-containing genes are maximally expressed (boldface arrow) by the Ino2-Ino4 activator complex. (Inset) Localization of Opi1, fused with GFP at its C-terminal end and integrated into the chromosome, being expressed under its own promoter in live cells growing logarithmically in synthetic complete medium lacking inositol (−Ins) and analyzed by fluorescence microscopy. (B) Growth conditions (e.g., stationary phase, inositol supplementation, or zinc depletion) under which the levels of PA are reduced, Opi1 dissociates from the nuclear/ER membrane, and enters into the nucleus where it binds to Ino2 and attenuates (thin arrow) transcriptional activation by the Ino2–Ino4 complex. (Inset) Localization of Opi1, as described in A, except that the cells are growing logarithmically in medium containing 75 μM inositol. PA level decreases by the stimulation of PI synthesis in response to inositol (Ins) supplementation and by Zap1-mediated induction of PIS1, that results in an increase in PI synthesis in response to zinc depletion. The regulation in response to zinc depletion and stationary phase occurs without inositol supplementation. Pah1 and Dgk1 play important roles in controlling PA content and transcriptional regulation of UAS_INO-containing genes. The synthesis of TAG (which is stored in lipid droplets, LD) and phospholipids (with the exception of PE, which occurs in the mitochondria and Golgi) occurs in the ER. Fluorescence microscopy images of Opi1 localization courtesy of Yu-Fang Chang, Henry Laboratory, Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY.