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Inositol pyrophosphates: between signalling and metabolism
Abstract
The present review will explore the insights gained into inositol pyrophosphates in the 20 years since their discovery in 1993. These molecules are defined by the presence of the characteristic 'high energy' pyrophosphate moiety and can be found ubiquitously in eukaryotic cells. The enzymes that synthesize them are similarly well distributed and can be found encoded in any eukaryote genome. Rapid progress has been made in characterizing inositol pyrophosphate metabolism and they have been linked to a surprisingly diverse range of cellular functions. Two decades of work is now beginning to present a view of inositol pyrophosphates as fundamental, conserved and highly important agents in the regulation of cellular homoeostasis. In particular it is emerging that energy metabolism, and thus ATP production, is closely regulated by these molecules. Much of the early work on these molecules was performed in the yeast Saccharomyces cerevisiae and the social amoeba Dictyostelium discoideum, but the development of mouse knockouts for IP6K1 and IP6K2 [IP6K is IP6 (inositol hexakisphosphate) kinase] in the last 5 years has provided very welcome tools to better understand the physiological roles of inositol pyrophosphates. Another recent innovation has been the use of gel electrophoresis to detect and purify inositol pyrophosphates. Despite the advances that have been made, many aspects of inositol pyrophosphate biology remain far from clear. By evaluating the literature, the present revi…
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“I(1,4,5)P3 is also a substrate for the synthesis of inositol polyphosphates including pyro-phosphates such as IP7 and IP8 which are recognised as signalling molecules, including metabolic messengers or energy sensors [50].”
From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [50]
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Diphospho‐myo‐inositol phosphates during the life cycle of Dictyostelium and Polysphondylium
Laußmann, T., Pikzack, C., Thiel, U., Mayr, G. W., & Vogel, G. (2000) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2000.01264.x · Cited by 42
Accumulation of [3H]-inositol into inositol polyphosphates during development of Dictyostelium
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The Role of Phosphoinositide Metabolism in Signal Transduction in Secretory Cells
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First synthetic analogues of diphosphoinositol polyphosphates: interaction with PP-InsP5 kinase
Riley, A. M., Wang, H., Weaver, J. D., Shears, S. B., & Potter, B. V. L. (2012) · Chemical Communications · doi:10.1039/c2cc36044f · Cited by 35
Laußmann, T., Hansen, A., Reddy, K. M., Reddy, K. K., Falck, J. R., & Vogel, G. (1998) · FEBS Letters · doi:10.1016/s0014-5793(98)00329-9 · Cited by 34
Inositol Hexakisphosphate Kinases Induce Cell Death in Huntington Disease
Nagata, E., Saiardi, A., Tsukamoto, H., Okada, Y., Itoh, Y., Satoh, T., Itoh, J., Margolis, R. L., Takizawa, S., Sawa, A., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.220749 · Cited by 33
Self-citationInositol hexakisphosphate kinase-2 acts as an effector of the vertebrate Hedgehog pathway
Sarmah, B., & Wente, S. R. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1007256107 · Cited by 32
Taylor, Jr., Chen, P.-H., Chou, C.-C., Patel, J., & Jin, S. V. (2012) · Autophagy · doi:10.4161/auto.20681 · Cited by 32
Barbara, K. E., Haley, T. M., Willis, K. A., & Santangelo, G. M. (2006) · Molecular Genetics and Genomics · doi:10.1007/s00438-006-0182-0 · Cited by 32
Inositol hexakisphosphate kinases promote autophagy
Nagata, E., Saiardi, A., Tsukamoto, H., Satoh, T., Itoh, Y., Itoh, J., Shibata, M., Takizawa, S., & Takagi, S. (2010) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2010.09.013 · Cited by 28
Self-citationBanfíƈ, H., Bedalov, A., York, J. D., & Višnjić, D. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.412288 · Cited by 27
Downes, C. P., Gray, A., Fairservice, A., Safrany, S. T., Batty, I. H., & Fleming, I. N. (2005) · Biochemical Society Transactions · doi:10.1042/bst0331303 · Cited by 27
Mitochondrial function, mitochondrial DNA and ageing: a reappraisal
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Preparation of Quality Inositol Pyrophosphates
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Self-citationStructure and Function of Inositol 1,4,5‐Trisphosphate Receptor
Mikoshiba, K., Furuichi, T., Miyawaki, A., Yoshikawa, S., Nakade, S., Michikawa, T., Nakagawa, T., Okano, H., Kume, S., MUTO, A., et al. (1993) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1993.tb38052.x · Cited by 24
The signaling role of inositol hexakisphosphate kinases (IP6Ks)
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Self-citationHorigome, C., Ikeda, R., Okada, T., Takenami, K., & Mizuta, K. (2009) · Bioscience Biotechnology and Biochemistry · doi:10.1271/bbb.80599 · Cited by 16
Flagged first, then by citations
1 of the 122 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Resnick, 2009, Inositol phosphates, 1
Cited by
Sorted by citations
Inositol Pyrophosphate InsP8 Acts as an Intracellular Phosphate Signal in Arabidopsis
Dong, J., Ma, G., Sui, L., Wei, M., Satheesh, V., Zhang, R., Ge, S., Li, J., Zhang, T., Wittwer, C., et al. (2019) · Molecular Plant · doi:10.1016/j.molp.2019.08.002 · Cited by 274
An inside-out origin for the eukaryotic cell
Baum, D., & Baum, B. (2014) · BMC Biology · doi:10.1186/s12915-014-0076-2 · Cited by 218
THOMAS, M. P., Mills, S. J., & Potter, B. V. L. (2015) · Angewandte Chemie International Edition · doi:10.1002/anie.201502227 · Cited by 191
Protein Polyphosphorylation of Lysine Residues by Inorganic Polyphosphate
Azevedo, C., Livermore, T. M., & Saiardi, A. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.02.010 · Cited by 186
Self-citationPhosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane
Katan, M., & Cockcroft, S. (2020) · Essays in Biochemistry · doi:10.1042/ebc20200041 · Cited by 176
Metadata
- Authors
- Wilson, M. S. C., Livermore, T. M., & Saiardi, A.
- Affiliations
- MRC Laboratory for Molecular Cell Biology (GB)
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2013-05-31
- Volume
- 452
- Issue
- 3
- Pages
- 369-379
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- OpenAlex
- W1990899386
- Cited by
- 256
- References
- 122
- Citations by year
- 2026: 7 · 2025: 16 · 2024: 14 · 2023: 20 · 2022: 18 · 2021: 19 · 2020: 25 · 2019: 25 · 2018: 15 · 2017: 23 · 2016: 28 · 2015: 24 · 2014: 15 · 2013: 7
- FWCI
- 2.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical Journal (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Medical Research Council (MC_UU_12018/4)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Keywords
- inositol pyrophosphates, phytic acid, IP6K1, energy metabolism, cellular homeostasis, ATP production, Saccharomyces cerevisiae, Dictyostelium discoideum, mouse knockout models
- MeSH terms
- Animals, Energy Metabolism, Humans, Inositol Phosphates, Diphosphates, Signal Transduction, Phosphotransferases (Phosphate Group Acceptor)
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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