Abstract
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.
Highlights
Inorganic phosphate (Pi) is a simple chemical element essential for ATP formation through glycolysis, gluconeogenesis, or energy metabolism or as a constituent of DNA, RNA, phospholipids, and a variety of phosphorylated metabolic intermediates [1,2,3,4]
We highlight studies regarding the ability of Pi to induce the production of reactive oxygen species (ROS) and regulate several pathophysiological processes that result from different sources producing ROS, which are generally reversed by the addition of different antioxidants or when Pi uptake is inhibited in the cytoplasm and mitochondria
Sci. 2021, 22, 7768 of ROS and regulate several pathophysiological processes that result from different sources producing ROS, which are generally reversed by the addition of different antioxidants or when Pi uptake is inhibited in the cytoplasm and mitochondria
Summary
Inorganic phosphate (Pi) is a simple chemical element essential for ATP formation through glycolysis, gluconeogenesis, or energy metabolism or as a constituent of DNA, RNA, phospholipids, and a variety of phosphorylated metabolic intermediates [1,2,3,4]. FGF-23 is produced in bone by osteocytes, whereas the parathyroid glands produce PTH Both hormones activate their specific receptors on the proximal renal tubules to reduce the apical expression of the cotransporters NaPi-IIa and NaPi-IIc. PTH further increases the expression of the renal 1-α hydroxylase necessary for vitamin D production, while FGF-23 inhibits it. A low expression of transmembrane-α-klotho is generally associated with kidney tubular cell resistance to FGF23, leading to hyperphosphatemia [10]. Regarding reactive oxygen species (ROS), H2O2 and O2−, are key redox signalling agents generated mainly by NADPH oxidases (NOX) and the mitochondrial electron transport chain (ETC) [13,14,15]. We highlight studies regarding the ability of Pi to induce the production of ROS and regulate several pathophysiological processes that result from different sources producing ROS, which are generally reversed by the addition of different antioxidants or when Pi uptake is inhibited in the cytoplasm and mitochondria
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