The response to inositol: Regulation of glycerolipid metabolism and stress response signaling in yeast

Abstract

This article focuses on discoveries of the mechanisms governing the regulation of glycerolipid metabolism and stress response signaling in response to the phospholipid precursor, inositol. The regulation of glycerolipid lipid metabolism in yeast in response to inositol is highly complex, but increasingly well understood, and the roles of individual lipids in stress response are also increasingly well characterized. Discoveries that have emerged over several decades of genetic, molecular and biochemical analyses of metabolic, regulatory and signaling responses of yeast cells, both mutant and wild type, to the availability of the phospholipid precursor, inositol are discussed.

Characterization of the S. cerevisiae inp51 mutant links phosphatidylinositol 4,5-bisphosphate levels with lipid content, membrane fluidity and cold growth

“…1) [41]. PI(4,5)P 2 is a relatively common phospholipid, that plays key regulatory roles in a number of essential cellular processes [29,64], including ion channel modulation [101], cytoskeletal regulation [88,112], endocytosis of plasma membrane proteins [103] and membrane identity [38].…”

Lipid metabolic changes in an early divergent fungus govern the establishment of a mutualistic symbiosis with endobacteria

“…It is unclear, however, why fungi would accumulate TAG during symbiosis establishment, when a more plausible progression would be to break down TAG to release the energy source for bacteria. An alternative explanation is that the accumulation of TAG and PE during symbiosis establishment could be a result of transient accumulation of their precursor PA. PA is known to have signaling roles in eukaryotes (18) and it is possible that an accumulation of PA, undetected in this study, serves a signaling function in the coordination of symbiosis establishment. Accumulation of TAG and PE could thus be the end result of transient accumulation of PA, which, upon serving its signaling function, could become converted into PE through the cytidine diphosphate (CDP)-DAG pathway and channeled into biosynthesis of TAG by first becoming converted into DAG via a PA phosphatase.…”

“…1). Central intermediates of this pathway are diacylglycerol (17,18). They are interconvertible, i.e., PA can be dephosphorylated by a PA phosphatase to produce DAG (19), and DAG can be phosphorylated by DAG kinase (DGK) to yield PA (20).…”

Interaction between repressor Opi1p and ER membrane protein Scs2p facilitates transit of phosphatidic acid from the ER to mitochondria and is essential for INO1 gene expression in the presence of choline

“…2, A and B) and is suppressed by mutations in the CDP-choline pathway for PC biosynthesis (17,18). The opi1⌬ mutation, in contrast, confers constitutive overexpression of INO1 and other UAS INO -containing genes (3)(4)(5)33), resulting in overproduction and excretion of inositol into the growth medium (Opi Ϫ phenotype). The opi1⌬ mutant also exhibits a Pet Ϫ phenotype (i.e.…”