Eukaryotic Phosphate Homeostasis: The Inositol Pyrophosphate Perspective. Issue 3 (March 2017)

• Record Type: Journal Article
• Authors: Azevedo, Cristina; Saiardi, Adolfo
• Is Part Of: Trends in biochemical sciences. Volume 42:Issue 3(2017)
• Page Start: 219
• Page End: 231
• Publication Date: 2017-03
• Subjects: metabolism -- signaling -- inositol pyrophosphates -- inorganic polyphosphate -- SPX domain -- phosphate; Biochemistry -- Periodicals; 572
• DOI: 10.1016/j.tibs.2016.10.008
• Languages: English
• ISSNs: 0968-0004

Abstract

Abstract : Phosphate, as a cellular energy currency, essentially drives most biochemical reactions defining living organisms, and thus its homeostasis must be tightly regulated. Investigation into the role of inositol pyrophosphates (PP-IPs) has provided a novel perspective on the regulation of phosphate homeostasis. Recent data suggest that metabolic and signaling interplay between PP-IPs, ATP, and inorganic polyphosphate (polyP) influences and is influenced by cellular phosphate homeostasis. Different studies have demonstrated that the SPX protein domain is a key component of proteins involved in phosphate metabolism. How PP-IPs control some aspects of phosphate homeostasis has become clearer with the recently acquired crystal structures of SPX domains. We review here recent studies on eukaryote phosphate homeostasis and provide insights into future research. Trends: Many proteins involved in phosphate metabolism contain an SPX domain, raising the possibility that this domain may sense cellular phosphate status. The recently resolved structure of several SPX domains revealed the presence of a basic binding region that recognizes PP-IPs. The binding of these molecules to the SPX domains of the VTC protein complex stimulated inorganic polyP synthesis. Changes in phosphate availability alter ATP and PP-IP levels allowing them to transduce cellular phosphate status. Phosphate homeostasis is also controlled by the ability of PP-IPs to regulate basic metabolism. The relative abundance, synthesis, and regulation of PP-IPs, ATP, and inorganic polyP are interconnected, affecting phosphate homeostasis and thus primary metabolism.