Abstract
In yeast, inositol biosynthesis is coordinated with the synthesis of phospholipids by controlling the expression of enzymes in the biosynthetic pathways. Inositol pyrophosphates, most recently characterized in the inositide family, have diverse roles in phosphate signaling and other important cellular processes. However, little is known about the function of inositol pyrophosphates in the biosynthesis of inositol and phospholipids. The objective of this study is to understand the mechanistic links between inositol metabolism and inositol pyrophosphates. Our results indicated that inositol pyrophosphate deficient mutants kcs1Δ and vip1Δ exhibit decreased inositol biosynthesis due to decreased derepression of INO1, which encodes the rate‐limiting enzyme for inositol biosynthesis. Further studies revealed that the inositol pyrophosphate kinase activity and the basic leucine zipper (bZIP) domains in KCS1 are both required for optimal INO1 expression. Interestingly, the levels of Kcs1p correlate with INO1 expression. We conclude that conversion of IP5 to inositol pyrophosphates modulates INO1 transcription.This work is funded by grant R01 DK081367 from NIH and a travel grant from Wayne State University.
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