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Cell Rep. 2017 Jul 25;20(4):895-908. doi: 10.1016/j.celrep.2017.06.082.

Glycolytic Enzymes Coalesce in G Bodies under Hypoxic Stress.

Author information

1
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
2
Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
3
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
4
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
5
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
6
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
7
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
8
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
9
Research Institute for Science and Technology, Kogakuin University, Hachioji, Tokyo 192-0015, Japan.
10
Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
11
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Division of Nephrology, Department of Molecular and Integrative Physiology and the Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
12
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: klionsky@umich.edu.
13
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA. Electronic address: jnkim@jhu.edu.

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.

KEYWORDS:

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

PMID:
28746874
PMCID:
PMC5586494
DOI:
10.1016/j.celrep.2017.06.082
[Indexed for MEDLINE]
Free PMC Article

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