Phosphocitrate inhibits mitochondrial and cytosolic accumulation of calcium in kidney cells in vivo

W. P. Tew, C. D. Malis, J. E. Howard, A. L. Lehninger

Research output: Contribution to journalArticlepeer-review

Abstract

Synthetic 3-phosphocitrate, an extremely potent inhibitor of calcium phosphate crystallization as determined in a nonbiological physical-chemical assay, has many similarities to a mitochondrial factor that inhibits crystallization of nondiffracting amorphous calcium phosphate. In order to determine whether phosphocitrate can prevent uptake and crystallization of calcium phosphate in mitochondria in vivo, it was administered intraperitoneally to animals given large daily doses of calcium gluconate or parathyroid hormone, a regimen that causes massive accumulation and crystallization of calcium phosphate in the mitochondria and cytosol of renal tubule cells in vivo. Administration of phosphocitrate greatly reduced the net uptake of Ca2+ by the kidneys and prevented the appearance of apatite-like crystalline structures within the mitochondrial matrix and cytosol of renal tubule cells. Phosphocitrate, which is a poor chelator of Ca2+, did not reduce the hypercalcemia induced by either agent. These in vivo observations therefore indicate that phosphocitrate acts primarily at the cellular level to prevent the extensive accumulation of calcium phosphate in kidney cells by inhibiting the mitochondrial accumulation or crystallization of calcium phosphate.

Original languageEnglish (US)
Pages (from-to)5528-5532
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume78
Issue number9 II
DOIs
StatePublished - 1981

ASJC Scopus subject areas

  • General

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