Inorganic Polyphosphates in the Mitochondria of Mammalian Cells
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
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Inorganic Polyphosphates in the Mitochondria of Mammalian Cells Lea K. Seidlmayer and Elena N. Dedkova
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 polybeta-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
L.K. Seidlmayer Department of Internal Medicine 1, University Hospital Wuerzburg, Oberduerrbacherstr. 6, 97080 Wuerzburg, Germany e-mail: [email protected] E.N. Dedkova, DVM, PhD (*) Department of Pharmacology, University of California at Davis, 451 E. Health Sciences Drive, Davis, CA 95616, USA e-mail: [email protected] © Springer International Publishing Switzerland 2016 T. Kulakovskaya et al. (eds.), Inorganic Polyphosphates in Eukaryotic Cells, DOI 10.1007/978-3-319-41073-9_7
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L.K. Seidlmayer and E.N. Dedkova
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.
Abbreviations [Ca2+]em Extramitochondrial Ca2+ concentration [Ca2+]m Mitochondrial Ca2+ concentration Ca2+ Calcium FCCP Carbonyl cyanide p-trifluoromethoxyphenylhydrazone HF Heart failure MCU Mitochondrial Ca2+ uniporter mPTP Mitochondrial permeability transition pore PHB Poly-β-hydroxybutyrate polyP Inorganic polyphosphate PPX Exopolyphosphatase enzyme ROS Reactive oxygen species TMPD Tetramethyl-p-phenylenediamine TMRM Tetramethylrhodamine, methyl ester
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Introduction
Inorganic polyphosphates (polyPs) are linear polymers of orthophosphate (Pi) residues linked through the common oxygen atoms by high-energy phosphoanhydride bonds similar to adenos
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