Glycolytic Enzymes Coalesce in G Bodies under Hypoxic Stress

Meiyan Jin, Ting Han, Yao Yao, Amelia F. Alessi, Mallory A. Freeberg, Ken Inoki, Daniel J. Klionsky, John K. Kim, Meiyan Jin, Daniel J. Klionsky, Ting Han, Mallory A. Freeberg, Alla Karnovsky, James J. Moresco, John R. Yates, Misuzu Baba, Aaron D. Gitler, Ken Inoki, Gregory G. Fuller, Amelia F. AlessiMallory A. Freeberg, Nathan P. Roach, John K. Kim, Ting Han

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Glycolysis is upregulated under conditions such as hypoxia and high energy demand to promote cell proliferation, although the mechanism remains poorly understood. We find that hypoxia in Saccharomyces cerevisiae induces concentration of glycolytic enzymes, including the Pfk2p subunit of the rate-limiting phosphofructokinase, into a single, non-membrane-bound granule termed the “glycolytic body” or “G body.” A yeast kinome screen identifies the yeast ortholog of AMP-activated protein kinase, Snf1p, as necessary for G-body formation. Many G-body components identified by proteomics are required for G-body integrity. Cells incapable of forming G bodies in hypoxia display abnormal cell division and produce inviable daughter cells. Conversely, cells with G bodies show increased glucose consumption and decreased levels of glycolytic intermediates. Importantly, G bodies form in human hepatocarcinoma cells in hypoxia. Together, our results suggest that G body formation is a conserved, adaptive response to increase glycolytic output during hypoxia or tumorigenesis.

Original languageEnglish (US)
Pages (from-to)895-908
Number of pages14
JournalCell Reports
Volume20
Issue number4
DOIs
StatePublished - Jul 25 2017

Keywords

  • RNA binding protein
  • RNA granule
  • glycolysis
  • hypoxia
  • intrinsically disordered region
  • phase transitions

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Jin, M., Han, T., Yao, Y., Alessi, A. F., Freeberg, M. A., Inoki, K., Klionsky, D. J., Kim, J. K., Jin, M., Klionsky, D. J., Han, T., Freeberg, M. A., Karnovsky, A., Moresco, J. J., Yates, J. R., Baba, M., Gitler, A. D., Inoki, K., Fuller, G. G., ... Han, T. (2017). Glycolytic Enzymes Coalesce in G Bodies under Hypoxic Stress. Cell Reports, 20(4), 895-908. https://doi.org/10.1016/j.celrep.2017.06.082