Inorganic Polyphosphates As Storage for and Generator of Metabolic Energy in the Extracellular Matrix

Abstract

Inorganic polyphosphates (polyP) consist of linear chains of orthophosphate residues, linked by high-energy phosphoanhydride bonds. They are evolutionarily old biopolymers that are present from bacteria to man. No other molecule concentrates as much (bio)chemically usable energy as polyP. However, the function and metabolism of this long-neglected polymer are scarcely known, especially in higher eukaryotes. In recent years, interest in polyP experienced a renaissance, beginning with the discovery of polyP as phosphate source in bone mineralization. Later, two discoveries placed polyP into the focus of regenerative medicine applications. First, polyP shows morphogenetic activity, i.e., induces cell differentiation via gene induction, and, second, acts as an energy storage and donor in the extracellular space. Studies on acidocalcisomes and mitochondria provided first insights into the enzymatic basis of eukaryotic polyP formation. In addition, a concerted action of alkaline phosphatase and adenylate kinase proved crucial for ADP/ATP generation from polyP. PolyP added extracellularly to mammalian cells resulted in a 3-fold increase of ATP. The importance and mechanism of this phosphotransfer reaction for energy-consuming processes in the extracellular matrix are discussed. This review aims to give a critical overview about the formation and function of this unique polymer that is capable of storing (bio)chemically useful energy.

Development and Characterization of Acidic-pH Tolerant Mutants of Zymomonas mobilis through Adaptation and Next Generation Sequencing based Genome Resequencing and RNA-Seq

“…Several biological functions have been identified for cellular polyP including buffering capacities for pH homeostasis, DNA damage repair, cell cycle, motility, and biofilm formation [49][50][51]. Studies in other bacteria showed that polyP was rapidly accumulated by PPK under environmental stresses including acidic conditions [52][53][54]. Our transcriptomic data indicated that the expression of ppk in wild-type ZM4 was upregulated under acidic pH compared with neutral pH (Table S2), which is consistent with above reported conclusion.…”

Development and Characterization of Acidic-pH Tolerant Mutants of Zymomonas mobilis through Adaptation and Next Generation Sequencing based Genome Resequencing and RNA-Seq

“…Several biological functions have been identi ed for cellular polyP including buffering capacities for pH homeostasis, DNA damage repair, cell cycle, motility, and bio lm formation [48][49][50]. Studies in other bacteria showed that polyP was rapidly accumulated by PPK under environmental stresses including acidic conditions [51][52][53]. Our transcriptomic data indicated that the expression of ppk in wild-type ZM4 and mutant strains was upregulated at pH 3.8 compared with pH 6.2 (Table S2), which is consistent with the conclusion reported above.…”

The biomaterial polyphosphate blocks stoichiometric binding of the SARS-CoV-2 S-protein to the cellular ACE2 receptor

“…It has been pointed out that polyP has a high degree of rotational flexibility, paralleled with various conformations, like staggered or eclipsed, which depend on the arrangement of the tetrahedral PO 4 units. 13,43 Modification of Arg with 1,2-cyclohexanedione…”

“…12 Now during the search for compounds acting as potential inhibitors of SARS-CoV-2 infection that might gain therapeutic impact, we studied the effects of the natural polymers of polyP (reviewed in: ref. 13) andin comparisonof heparin on the binding of the virus to the target cells. A model system was applied for these studies, a binding assay, in which the cellular receptor for SARS-CoV-2, the recombinant angiotensin-converting enzyme 2 (ACE2), 14 was attached to the well plate and the labeled receptor-binding domain (RBD) of the SARS-CoV-2 spike (S)-protein was used as a detector molecule.…”