Journal article

In the absence of apoptosis, myeloid cells arrest when deprived of growth factor, but remain viable by consuming extracellular glucose

Li Dong, Boris Reljic, Jen G Cheung, Elizabeth S Ng, Lisa M Lindqvist, Andrew G Elefanty, David L Vaux, Hoanh Tran

Cell Death & Differentiation | NATURE PUBLISHING GROUP | Published : 2019

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 tha..

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Grants

Awarded by Australian National Health and Medical Research Council (NHMRC) Program


Awarded by NHMRC


Awarded by Leukemia and Lymphoma Society SCOR grant


Funding Acknowledgements

We thank Gabriela Brumatti, Rebecca Feltham, James Vince, Simon Monard, David Huang, and Andre Samson for discussion, technical advice, and reagents. Funding for this project was provided by the Australian National Health and Medical Research Council (NHMRC) Program Grant #1113133 and NHMRC fellowship 1020136 to DLV; and the Leukemia and Lymphoma Society SCOR grant #7001-13. Work in the authors' laboratory is made possible by operational infrastructure grants through the Australian Government Independent Research Institutes Infrastructure Support (IRISS) and the Victorian State Government OIS.