Glycolytic Enzymes Coalesce in G Bodies under Hypoxic Stress

Publication date: 25 July 2017
Source:Cell Reports, Volume 20, Issue 4
Author(s): Meiyan Jin, Gregory G. Fuller, Ting Han, Yao Yao, Amelia F. Alessi, Mallory A. Freeberg, Nathan P. Roach, James J. Moresco, Alla Karnovsky, Misuzu Baba, John R. Yates, Aaron D. Gitler, Ken Inoki, Daniel J. Klionsky, John K. Kim
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.

Graphical abstract

Teaser

Jin et al. find that hypoxia leads to concentration of glycolytic enzymes into foci referred to as "G bodies" in S. cerevisiae and human hepatocarcinoma cells. G-body formation is a conserved, facultative response that may help cells survive and proliferate under low oxygen conditions.


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