Glycolytic Enzymes Coalesce in G Bodies under Hypoxic Stress

作者:Jin Meiyan; Fuller Gregory G; Han Ting; Yao Yao; Alessi Amelia F; Freeberg Mallory A; Roach Nathan P; Moresco James J; Karnovsky Alla; Baba Misuzu; Yates John R III; Gitler Aaron D; Inoki Ken; Klionsky Daniel J; Kim John K
来源:Cell Reports, 2017, 20(4): 895-908.
DOI:10.1016/j.celrep.2017.06.082

摘要

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-membranebound 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 proteomicsare 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.

  • 出版日期2017-7-25