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• W2912088832 endingPage "2085" @default.
• W2912088832 startingPage "2074" @default.
• W2912088832 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 double mutant 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 When serum was withdrawn, the provision of an equivalent amount of glucose present in 10% FBS (~0.5 mM) was sufficient to support cell survival for more than a week, in the presence or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." @default.
• W2912088832 created "2019-02-21" @default.
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• W2912088832 date "2019-02-15" @default.
• W2912088832 modified "2023-10-07" @default.
• W2912088832 title "In the absence of apoptosis, myeloid cells arrest when deprived of growth factor, but remain viable by consuming extracellular glucose" @default.
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• W2912088832 doi "https://doi.org/10.1038/s41418-019-0275-z" @default.
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