In the absence of apoptosis, myeloid cells arrest when deprived of growth factor, but remain viable by consuming extracellular glucose
- Author(s)
- Dong, L; Reljic, B; Cheung, JG; Ng, ES; Lindqvist, LM; Elefanty, AG; Vaux, DL; Tran, H;
- 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 When serum was withdrawn, the provision of an equivalent amount of glucose present in 10% FBS (~0.5 mM) was sufficient to support cell survival for more than a week, in the presence or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
- Research Division(s)
- Inflammation
- PubMed ID
- 30770875
- Publisher's Version
- https://doi.org/10.1038/s41418-019-0275-z
- NHMRC Grants
- NHMRC/1113133, NHMRC/1020136,
- Terms of Use/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