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.