Phosphate sensing in health and disease

Christoph Zechner, Eugene P. Rhee

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

Abstract

Purpose of reviewDisruptions of phosphate homeostasis are associated with a multitude of diseases with insufficient treatments. Our knowledge regarding the mechanisms underlying metazoan phosphate homeostasis and sensing is limited. Here, we highlight four major advancements in this field during the last 12-18 months.Recent findingsFirst, kidney glycolysis senses filtered phosphate, which results in the release of glycerol 3-phosphate (G-3-P). Circulating G-3-P then stimulates synthesis of the phosphaturic hormone fibroblast growth factor 23 in bone. Second, the liver serves as a postprandial phosphate reservoir to limit serum phosphate excursions. It senses phosphate ingestion and triggers renal excretion of excess phosphate through a nerve-dependent mechanism. Third, phosphate-starvation in cells massively induces the phosphate transporters SLC20A1/PiT1 and SLC20A2/PiT2, implying direct involvement of cellular phosphate sensing. Under basal phosphate-replete conditions, PiT1 is produced but immediately destroyed, which suggests a novel mechanism for the regulation of PiT1 abundance. Fourth, Drosophila melanogaster intestinal cells contain novel organelles called PXo bodies that limit intracellular phosphate excursions. Phosphate starvation leads to PXo body dissolution, which triggers midgut proliferation.SummaryThese studies have opened novel avenues to dissect the mechanisms that govern metazoan phosphate sensing and homeostasis with the potential to identify urgently needed therapeutic targets.

Original languageEnglish (US)
Pages (from-to)361-367
Number of pages7
JournalCurrent opinion in nephrology and hypertension
Volume33
Issue number4
DOIs
StatePublished - Jul 1 2024

Keywords

  • FGF23
  • PXo
  • SLC20A1/PiT1
  • glycerol 3-phosphate
  • systemic and cell-autonomous phosphate sensing

ASJC Scopus subject areas

  • Internal Medicine
  • Nephrology

Fingerprint

Dive into the research topics of 'Phosphate sensing in health and disease'. Together they form a unique fingerprint.

Cite this