In the absence of apoptosis, myeloid cells arrest when deprived of growth factor, but remain viable by consuming extracellular glucose
- 15 February 2019
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death & Differentiation
- Vol. 26 (10), 2074-2085
- https://doi.org/10.1038/s41418-019-0275-z
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 When serum was withdrawn, the provision of an equivalent amount of glucose present in 10% FBS (~0.5 mM) was sufficient to support cell survival for more than a week, in the presence or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.Funding Information
- Department of Health | National Health and Medical Research Council (1113133)
- Leukemia and Lymphoma Society (7001-13)
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