Abstract
Inorganic polyphosphate (polyP) is a polymer present in all living organisms. Although polyP is found to be involved in a variety of functions in cells of higher organisms, the enzyme responsible for polyP production and consumption has not yet been identified. Here, we studied the effect of polyP on mitochondrial respiration, oxidative phosphorylation and activity of F0F1-ATPsynthase. We have found that polyP activates mitochondrial respiration which does not coupled with ATP production (V2) but inhibits ADP-dependent respiration (V3). Moreover, PolyP can stimulate F0F1-ATPase activity in the presence of ATP and, importantly, can be hydrolyzed in this enzyme instead of ATP. Furthermore, PolyP can be produced in mitochondria in the presence of substrates for respiration and phosphate by the F0F1-ATPsynthase. Thus, polyP is an energy molecule in mammalian cells which can be produced and hydrolyzed in the mitochondrial F0F1-ATPsynthase.
Highlights
Inorganic polyphosphate is the oldest polymer found in living nature
It was shown that the level of inorganic polyphosphates in the cells is directly coupled to the mitochondrial metabolism [19]
Our data are in agreement with previously published data on the effect of polyP on the activity of plasma membrane Ca2+ATPase [30]
Summary
Inorganic polyphosphate ( polyP) is the oldest polymer found in living nature. It consists of a large number of orthophosphate residues which are connected by high energy bonds. In lower organisms, it is used for many functions and kept at very high concentrations as an energy source [1,2]. Regardless of the relatively low concentration of polyP in mammalian cells (up to 100 mM) compared with those in yeast or bacteria, this polymer has been shown to play an important role in physiology as well as in the development of different pathologies in higher organisms [3,4,5]. A transgenic mice overexpressing exopolyphosphatase from yeast, which reduce polyP to very low or almost non-detectable levels of this polymer in all cells, exhibited a phenotype with enhanced lactic acid production and reduced ATP levels [10]
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