Degradation of phosphate polymer polyP enhances lactic fermentation in mice

Nakamura, Akihiro; Kawano, Naoki; Motomura, Kei; Kuroda, Akio; Sekiguchi, Kazuma; Miyado, Mami; Kang, Woojin; Miyamoto, Yoshitaka; Hanai, Maito; Iwai, Maki; Yamada, Mitsutoshi; Hamatani, Toshio; Saito, Toki; Saito, Hidekazu; Tanaka, Mamoru; Umezawa, Akihiro; Miyado, Kenji

doi:10.1111/gtc.12639

Cited by 9 publications

(8 citation statements)

References 32 publications

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“…In this regard, the depletion of mitochondrial polyPs (through the overexpression and the activity of yeast PPX) significantly increased the levels of orthophosphates in the mitochondrial matrix (which is necessary for Ca 2+ binding), thus resulting in a decreased mitochondrial membrane potential and the inhibition of complex I of the respiratory chain (34,35). Thus, the crucial role of polyPs in cell metabolism is clear, as also confirmed in transgenic mice widely expressing the scPPX1 exopolyphosphatase that displayed a reduced mitochondrial respiration in muscles (36).…”

Section: Exopolyphosphatase (Ppx/ppase) Activitymentioning

confidence: 79%

Functional Genomics of PRUNE1 in Neurodevelopmental Disorders (NDDs) Tied to Medulloblastoma (MB) and Other Tumors

et al. 2021

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We analyze the fundamental functions of Prune_1 in brain pathophysiology. We discuss the importance and maintenance of the function of Prune_1 and how its perturbation influences both brain pathological conditions, neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies (NMIHBA; OMIM: 617481), and tumorigenesis of medulloblastoma (MB) with functional correlations to other tumors. A therapeutic view underlying recent discoveries identified small molecules and cell penetrating peptides to impair the interaction of Prune_1 with protein partners (e.g., Nm23-H1), thus further impairing intracellular and extracellular signaling (i.e., canonical Wnt and TGF-β pathways). Identifying the mechanism of action of Prune_1 as responsible for neurodevelopmental disorders (NDDs), we have recognized other genes which are found overexpressed in brain tumors (e.g., MB) with functional implications in neurodevelopmental processes, as mainly linked to changes in mitotic cell cycle processes. Thus, with Prune_1 being a significant target in NDDs, we discuss how its network of action can be dysregulated during brain development, thus generating cancer and metastatic dissemination.

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Section: Exopolyphosphatase (Ppx/ppase) Activitymentioning

confidence: 79%

Functional Genomics of PRUNE1 in Neurodevelopmental Disorders (NDDs) Tied to Medulloblastoma (MB) and Other Tumors

et al. 2021

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“…Further investigation has demonstrated that polyP, with an average chain length of 15 or longer, markedly enhances mTOR activation, which phosphorylates downstream molecules [ 7 ]. In transgenic mice expressing a polyP-degrading enzyme derived from budding yeast, the number of litters obtained by intercrossing male and female transgenic mice decreased [ 8 ]. This result implies that polyP may play a beneficial role in fertility.…”

Section: Introductionmentioning

confidence: 99%

Sodium Hexametaphosphate Serves as an Inducer of Calcium Signaling

et al. 2023

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In bacteria, polymers of inorganic phosphates, particularly linear polyphosphate, are used as alternative phosphate donors for adenosine triphosphate production. A six-chain form of sodium metaphosphate, sodium hexametaphosphate (SHMP), is believed to have no physiological functions in mammalian cells. In this study, we explored the possible effects of SHMP on mammalian cells, using mouse oocytes, which are useful for observing various spatiotemporal intracellular changes. Fertilization-competent oocytes were isolated from the oviducts of superovulated mice and cultured in an SHMP-containing medium. In the absence of co-incubation with sperm, SHMP-treated oocytes frequently formed pronuclei and developed into two-cell embryos owing to the increase in calcium concentration in the cytoplasm. We discovered an intriguing role for SHMP as an initiator of calcium rise in mouse oocytes, presumably in a wide variety of mammalian cells.

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“…abnormal levels of polyP have been found in cancer cells [7,8] and in neurons with familial forms (PINK1, LRRK2) of Parkinson's disease [9]. Interestingly, a transgenic mice overexpressing exopolyphosphatase from yeast, which ultimately reduce polyP to very low or almost non-detectable levels of this polymer in all cells, exhibited a phenotype with enhanced lactic acid production and reduced ATP levels [10].…”

Section: Introductionmentioning

confidence: 99%

Inorganic polyphosphate is produced and hydrolyzed in F0F1-ATP synthase of mammalian mitochondria

Baev¹,

Angelova

Abramov

2020

Biochemical Journal

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Inorganic polyphosphate (polyP) is a polymer present in all living organisms. Although polyP is found to be involved in a variety of functions in cells of higher organisms, the enzyme responsible for polyP production and consumption has not yet been identified. Here, we studied the effect of polyP on mitochondrial respiration, oxidative phosphorylation and activity of F0F1-ATPsynthase. We have found that polyP activates mitochondrial respiration which does not coupled with ATP production (V2) but inhibits ADP-dependent respiration (V3). Moreover, PolyP can stimulate F0F1-ATPase activity in the presence of ATP and, importantly, can be hydrolyzed in this enzyme instead of ATP. Furthermore, PolyP can be produced in mitochondria in the presence of substrates for respiration and phosphate by the F0F1-ATPsynthase. Thus, polyP is an energy molecule in mammalian cells which can be produced and hydrolyzed in the mitochondrial F0F1-ATPsynthase.

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Degradation of phosphate polymer polyP enhances lactic fermentation in mice

Cited by 9 publications

References 32 publications

Functional Genomics of PRUNE1 in Neurodevelopmental Disorders (NDDs) Tied to Medulloblastoma (MB) and Other Tumors

Functional Genomics of PRUNE1 in Neurodevelopmental Disorders (NDDs) Tied to Medulloblastoma (MB) and Other Tumors

Sodium Hexametaphosphate Serves as an Inducer of Calcium Signaling

Inorganic polyphosphate is produced and hydrolyzed in F0F1-ATP synthase of mammalian mitochondria

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