In the absence of apoptosis, myeloid cells arrest when deprived of growth factor, but remain viable by consuming extracellular glucose
Journal Title
Cell Death and Differentiation
Publication Type
Journal Article in press
Abstract
Withdrawal of the growth factor interleukin-3 (IL-3) from IL-3-dependent myeloid cells causes them to undergo Bax/Bak1-dependent apoptosis, whereas factor-deprived Bax(-/-)Bak1(-/-) cells remain viable, but arrest and shrink. It was reported that withdrawal of IL-3 from Bax(-/-)Bak1(-/-) cells caused decreased expression of the glucose transporter Glut1, leading to reduced glucose uptake, so that arrested cells required Atg5-dependent autophagy for long-term survival. In other cell types, a decrease in Glut1 is mediated by the thioredoxin-interacting protein (Txnip), which is induced in IL-3-dependent myeloid cells when growth factor is removed. We mutated Atg5 and Txnip by CRISPR/Cas9 and found that Atg5-dependent autophagy was not necessary for the long-term viability of cycling or arrested Bax(-/-)Bak1(-/-) cells, and that Txnip was not required for the decrease in Glut1 expression in response to IL-3 withdrawal. Surprisingly, Atg5-deficient Bax/Bak1 doublemutant cells survived for several weeks in medium supplemented with 10% fetal bovine serum (FBS), without high concentrations of added glucose or glutamine. When serum was withdrawn, the provision of an equivalent amount of glucose present in 10% FBS (~0.5 mM) was sufficient to support cell survival for more than a week, in the presence or absence of IL-3. Thus, Bax(-/-)Bak1(-/-) myeloid cells deprived of growth factor consume extracellular glucose to maintain long-term viability, without a requirement for Atg5-dependent autophagy.
Publisher
Springer Nature
WEHI Research Division(s)
Inflammation
PubMed ID
30770875
NHMRC Grants
NHMRC/1113133 NHMRC/1020136
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2019-03-13 11:54:09
Last Modified: 2019-03-13 01:57:37
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