Extracellular Inorganic Phosphate-Induced Release of Reactive Oxygen Species: Roles in Physiological Processes and Disease Development

Int J Mol Sci. 2021 Jul 21;22(15):7768. doi: 10.3390/ijms22157768.


Inorganic phosphate (Pi) is an essential nutrient for living organisms and is maintained in equilibrium in the range of 0.8-1.4 mM Pi. Pi is a source of organic constituents for DNA, RNA, and phospholipids and is essential for ATP formation mainly through energy metabolism or cellular signalling modulators. In mitochondria isolated from the brain, liver, and heart, Pi has been shown to induce mitochondrial reactive oxygen species (ROS) release. Therefore, the purpose of this review article was to gather relevant experimental records of the production of Pi-induced reactive species, mainly ROS, to examine their essential roles in physiological processes, such as the development of bone and cartilage and the development of diseases, such as cardiovascular disease, diabetes, muscle atrophy, and male reproductive system impairment. Interestingly, in the presence of different antioxidants or inhibitors of cytoplasmic and mitochondrial Pi transporters, Pi-induced ROS production can be reversed and may be a possible pharmacological target.

Keywords: hyperphosphataemia; inorganic phosphate; reactive oxygen species.

Publication types

  • Review

MeSH terms

  • Animals
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / pathology*
  • Diabetes Mellitus / etiology
  • Diabetes Mellitus / metabolism
  • Diabetes Mellitus / pathology*
  • Energy Metabolism
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / pathology*
  • Muscular Atrophy / etiology
  • Muscular Atrophy / metabolism
  • Muscular Atrophy / pathology*
  • Phosphates / pharmacology*
  • Reactive Oxygen Species / metabolism*


  • Phosphates
  • Reactive Oxygen Species