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The hexosamine biosynthetic pathway couples growth factor-induced glutamine uptake to glucose metabolism.

Abstract：

:Glucose and glutamine serve as the two primary carbon sources in proliferating cells, and uptake of both nutrients is directed by growth factor signaling. Although either glucose or glutamine can potentially support mitochondrial tricarboxylic acid (TCA) cycle integrity and ATP production, we found that glucose deprivation led to a marked reduction in glutamine uptake and progressive cellular atrophy in multiple mammalian cell types. Despite the continuous presence of growth factor and an abundant supply of extracellular glutamine, interleukin-3 (IL-3)-dependent cells were unable to maintain TCA cycle metabolite pools or receptor-dependent signal transduction when deprived of glucose. This was due at least in part to down-regulation of IL-3 receptor α (IL-3Rα) surface expression in the absence of glucose. Treatment of glucose-starved cells with N-acetylglucosamine (GlcNAc) to maintain hexosamine biosynthesis restored mitochondrial metabolism and cell growth by promoting IL-3-dependent glutamine uptake and metabolism. Thus, glucose metabolism through the hexosamine biosynthetic pathway is required to sustain sufficient growth factor signaling and glutamine uptake to support cell growth and survival.

journal_name

Genes Dev

journal_title

Genes & development

authors

Wellen KE,Lu C,Mancuso A,Lemons JM,Ryczko M,Dennis JW,Rabinowitz JD,Coller HA,Thompson CB

doi

10.1101/gad.1985910

subject

Has Abstract

pub_date

2010-12-15 00:00:00

pages

2784-99

issue

24

eissn

0890-9369

issn

1549-5477

pii

gad.1985910

journal_volume

24

pub_type

杂志文章

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