Phosphate Homeostasis − A Vital Metabolic Equilibrium Maintained Through the INPHORS Signaling Pathway

Cells face major changes in demand for and supply of inorganic phosphate (P(i)). P(i) is often a limiting nutrient in the environment, particularly for plants and microorganisms. At the same time, the need for phosphate varies, establishing conflicts of goals. Cells experience strong peaks of P(i) demand, e.g., during the S-phase, when DNA, a highly abundant and phosphate-rich compound, is duplicated. While cells must satisfy these P(i) demands, they must safeguard themselves against an excess of P(i) in the cytosol. This is necessary because P(i) is a product of all nucleotide-hydrolyzing reactions. An accumulation of P(i) shifts the equilibria of these reactions and reduces the free energy that they can provide to drive endergonic metabolic reactions. Thus, while P(i) starvation may simply retard growth and division, an elevated cytosolic P(i) concentration is potentially dangerous for cells because it might stall metabolism. Accordingly, the consequences of perturbed cellular P(i) homeostasis are severe. In eukaryotes, they range from lethality in microorganisms such as yeast (Sethuraman et al., 2001; Hürlimann, 2009), severe growth retardation and dwarfism in plants (Puga et al., 2014; Liu et al., 2015; Wild et al., 2016) to neurodegeneration or renal Fanconi syndrome in humans (Legati et al., 2015; Ansermet et al., 2017). Intracellular P(i) homeostasis is thus not only a fundamental topic of cell biology but also of growing interest for medicine and agriculture.