Degradation of phosphate polymer polyP enhances lactic fermentation in mice

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

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Abstract

In bacteria, a polymer of inorganic phosphate (Pi) (inorganic polyphosphate; polyP) is enzymatically produced and consumed as an alternative phosphate donor for adenosine triphosphate (ATP) production to protect against nutrient starvation. In vertebrates, polyP has been dismissed as a “molecular fossil” due to the lack of any known physiological function. Here, we have explored its possible role by producing transgenic (TG) mice widely expressing Saccharomyces cerevisiae exopolyphosphatase 1 (ScPPX1), which catalyzes hydrolytic polyP degradation. TG mice were produced and displayed reduced mitochondrial respiration in muscles. In female TG mice, the blood concentration of lactic acid was enhanced, whereas ATP storage in liver and brain tissues was reduced significantly. Thus, we suggested that the elongation of polyP reduces the intracellular Pi concentration, suppresses anaerobic lactic acid production, and sustains mitochondrial respiration. Our results provide an insight into the physiological role of polyP in mammals, particularly in females.

Original languageEnglish
Pages (from-to)904-914
Number of pages11
JournalGenes to Cells
Volume23
Issue number10
DOIs
Publication statusPublished - 2018 Oct

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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  • Cite this

    Nakamura, A., Kawano, N., Motomura, K., Kuroda, A., Sekiguchi, K., Miyado, M., Kang, W., Miyamoto, Y., Hanai, M., Iwai, M., Yamada, M., Hamatani, T., Saito, T., Saito, H., Tanaka, M., Umezawa, A., & Miyado, K. (2018). Degradation of phosphate polymer polyP enhances lactic fermentation in mice. Genes to Cells, 23(10), 904-914. https://doi.org/10.1111/gtc.12639