Inorganic Polyphosphates in the Mitochondria of Mammalian Cells

Abstract

This review discusses the current literature on existence and critical roles of the inorganic polyphosphate (polyP) in the mitochondria of mammalian cells. Inorganic polyP is a linear polymer of orthophosphate (Pi) residues linked together by high-energy phosphoanhydride bonds as in ATP. While the length of polyP chain can vary from a few phosphates to several thousands phosphate units long, only short-chain polyPs are detected in mammalian mitochondria. Mitochondrial Ca2+ is an essential signaling molecule required for the activation of Ca2+-dependent dehydrogenases and energy production; however, in excess, it could also trigger cell death. PolyP affects mitochondrial Ca2+-transporting systems and mitochondrial metabolism in several ways: (i) it is a potent activator of Ca2+-dependent mitochondrial permeability transition pore (mPTP) and possibly even compose Ca2+-transporting core of the mPTP via formation of the poly-beta-hydroxybutyrate (PHB)-Ca2+-polyP complex in the inner mitochondrial membrane; (ii) reduction of polyP levels increases mitochondrial Ca2+-uptake capacity and decreases the probability of the mPTP opening, and (iii) it is a chelator of Ca2+, among other divalent ions, and therefore it can modify mitochondrial matrix Ca2+-buffering capacity. Furthermore, changes in polyP levels can modulate mitochondrial bioenergetics, generation of the mitochondrial membrane potential, and ATP production by the F0F1-ATPase, which can also affect mitochondrial Ca2+-uptake capacity. PolyP concentration is dynamically changed during activation of the mitochondrial respiratory chain and stress conditions such as ischemia-reperfusion and heart failure indicating that polyP is an important component of the normal cell metabolism.