Inorganic Polyphosphate in Mammalian Cells and Tissues

Kumble, Krishnanand D.; Kornberg, Arthur

doi:10.1074/jbc.270.11.5818

Cited by 325 publications

(328 citation statements)

References 22 publications

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“…Confocal microscopy experiments showed co-localization of polyP and nucleolar markers (Figure 4). PolyP had previously been found in various other subcellular compartments, including mitochondria, 15 platelet dense granules, 6 and acidocalcisomes of unicellular organisms. …”

Section: Discussionmentioning

confidence: 99%

“…15 The procedure includes incubation with saturating RNAase and DNAase, and subsequent extractions with phenol/chloroform. Final concentrations of polyP were measured using purified recombinant yeast exopolyphosphatase (scPPX1), as described previously.…”

Section: Total Polyphosphate Isolation Polyphosphate Measurements Amentioning

confidence: 99%

“…© F e r r a t a S t o r t i F o u n d a t i o n concentrations of polyP in rat liver nuclei, have been reported, 15 but the distribution of the polyP within the organelle was not reported.…”

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confidence: 99%

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Myeloma cells contain high levels of inorganic polyphosphate which is associated with nucleolar transcription

Jimenez-Nuñez¹,

Moreno-Sanchez²,

Hernández-Ruiz³

et al. 2012

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundIn hematology there has recently been increasing interest in inorganic polyphosphate. This polymer accumulates in platelet granules and its functions include modulating various stages of blood coagulation, inducing angiogenesis, and provoking apoptosis of plasma cells. In this study we evaluated the characteristics of intracellular polyphosphate in myeloma cell lines, in primary myeloma cells from patients, and in other human B-cell populations from healthy donors. Design and MethodsWe have developed a novel flow cytometric method for detecting levels of polyphosphate in cell populations. We also used confocal microscopy and enzymatic analysis to study polyphosphate localization and characteristics. ResultsWe found that myeloma plasma cells contain higher levels of intracellular polyphosphate than normal plasma cells and other B-cell populations. Localization experiments indicated that high levels of polyphosphate accumulate in the nucleolus of myeloma cells. As the principal function of the nucleolus involves transcription of ribosomal DNA genes, we found changes in the cellular distribution of polyphosphate after the inhibition of nucleolar transcription. In addition, we found that RNA polymerase I activity, responsible for transcription in the nucleolus, is also modulated by polyphosphate, in a dose-dependent manner. ConclusionsOur results show an unusually high accumulation of polyphosphate in the nucleoli of myeloma cells and a functional relationship of this polymer with nucleolar transcription. Haematologica 2012;97(8):1264-1271. doi:10.3324/haematol.2011 This is an open-access paper. Myeloma cells contain high levels of inorganic polyphosphate which is associated with nucleolar transcription ABSTRACT© F e r r a t a S t o r t i F o u n d a t i o n

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Section: Discussionmentioning

confidence: 99%

Section: Total Polyphosphate Isolation Polyphosphate Measurements Amentioning

confidence: 99%

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Myeloma cells contain high levels of inorganic polyphosphate which is associated with nucleolar transcription

Jimenez-Nuñez¹,

Moreno-Sanchez²,

Hernández-Ruiz³

et al. 2012

Haematologica

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“…In S. cerevisiae, polyP is hydrolyzed through the combined action of an endopolyphosphatase and an exopolyphosphatase (39), which hydrolyze long-and short-chain polyP to polyP 3 and PP i . In Leishmania…”

Section: Role Of the N-terminal Extension In The Oligomerization Andmentioning

confidence: 99%

A Pyrophosphatase Regulating Polyphosphate Metabolism in Acidocalcisomes Is Essential for Trypanosoma brucei Virulence in Mice

Lemercier

Espiau

Ruiz

et al. 2004

Journal of Biological Chemistry

119

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“…PolyP has also been found in all higher eukaryotic organisms tested, where it is localized in various subcellular compartments, including mitochondria (4). Furthermore, mitochondrial polyP can form polyP/Ca 2ϩ /PHB complexes (5) with ion-conducting properties similar to those of native mitochondrial permeability transition pore (mPTP) (6).…”

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confidence: 99%

Targeted polyphosphatase expression alters mitochondrial metabolism and inhibits calcium-dependent cell death

Abramov

Fraley

Diao

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

198

178

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Polyphosphate (polyP) consists of tens to hundreds of phosphates, linked by ATP-like high-energy bonds. Although polyP is present in mammalian mitochondria, its physiological roles there are obscure. Here, we examine the involvement of polyP in mitochondrial energy metabolism and ion transport. We constructed a vector to express a mitochondrially targeted polyphosphatase, along with a GFP fluorescent tag. Specific reduction of mitochondrial polyP, by polyphosphatase expression, significantly modulates mitochondrial bioenergetics, as indicated by the reduction of inner membrane potential and increased NADH levels. Furthermore, reduction of polyP levels increases mitochondrial capacity to accumulate calcium and reduces the likelihood of the calcium-induced mitochondrial permeability transition, a central event in many types of necrotic cell death. This confers protection against cell death, including that induced by ␤-amyloid peptide, a pathogenic agent in Alzheimer's disease. These results demonstrate a crucial role played by polyP in mitochondrial function of mammalian cells. mitochondria ͉ permeability transition ͉ polyphosphate ͉ ␤-amyloid peptide ͉ necrosis T he chemical and physical properties of polyphosphate (polyP), including its high negative charge and its ability to form complexes with Ca 2ϩ and to form high energy bonds, underlie its potential to play an important role in cell metabolism. Significant amounts of polyP have been found in bacteria and in lower eukaryotes. In those organisms, it provides energy storage and a reserve pool of inorganic phosphate, participates in regulation of gene expression, protects cells from the toxicity of heavy metals by forming complexes with them, and participates in channel formation through assembly into complexes with Ca 2ϩ and polyhydroxybutyrate (PHB) (polyP/Ca 2ϩ /PHB complex) (1, 2) and possibly through interaction with channelforming proteins (3).PolyP has also been found in all higher eukaryotic organisms tested, where it is localized in various subcellular compartments, including mitochondria (4). Furthermore, mitochondrial polyP can form polyP/Ca 2ϩ /PHB complexes (5) with ion-conducting properties similar to those of native mitochondrial permeability transition pore (mPTP) (6). mPTP opening or formation in the mitochondrial inner membrane is believed to underlie the Ca 2ϩ -induced permeability transition (PT), a phenomenon that causes inner membrane depolarization and disruption of ATP synthesis and plays a central role during various types of necrotic and apoptotic cell death (7). The molecular composition of the conducting pathway of mPTP is currently not well defined.Recently, we have raised the possibility that, in vivo, the polyP/ Ca 2ϩ /PHB complex might comprise the ion-conducting part of the mPTP complex (6). If so, mitochondrial polyP should be essential for mPTP opening/formation. Here, we examine the involvement of polyP in normal mitochondrial function and in PT development during stress. To this end, we specifically reduced levels of mitocho...

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Inorganic Polyphosphate in Mammalian Cells and Tissues

Cited by 325 publications

References 22 publications

Myeloma cells contain high levels of inorganic polyphosphate which is associated with nucleolar transcription

Myeloma cells contain high levels of inorganic polyphosphate which is associated with nucleolar transcription

A Pyrophosphatase Regulating Polyphosphate Metabolism in Acidocalcisomes Is Essential for Trypanosoma brucei Virulence in Mice

Targeted polyphosphatase expression alters mitochondrial metabolism and inhibits calcium-dependent cell death

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