Glucose-starved cells do not engage in prosurvival autophagy

Ramirez-Peinado, S., Leon-Annicchiarico, C. L., Galindo-Moreno, J., Iurlaro, R., Caro-Maldonado, A., Prehn, J. H.M., Ryan, K. M. and Munoz-Pinedo, C. (2013) Glucose-starved cells do not engage in prosurvival autophagy. Journal of Biological Chemistry, 288(42), pp. 30387-30398. (doi:10.1074/jbc.M113.490581)

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Publisher's URL: http://dx.doi.org/10.1074/jbc.M113.490581

Abstract

In response to nutrient shortage or organelle damage, cells undergo macroautophagy. Starvation of glucose, an essential nutrient, is thought to promote autophagy in mammalian cells. We thus aimed to determine the role of autophagy in cell death induced by glucose deprivation. Glucose withdrawal induces cell death that can occur by apoptosis (in Bax, Bak-deficient mouse embryonic fibroblasts or HeLa cells) or by necrosis (in Rh4 rhabdomyosarcoma cells). Inhibition of autophagy by chemical or genetic means by using 3-methyladenine, chloroquine, a dominant negative form of ATG4B or silencing Beclin-1, Atg7, or p62 indicated that macroautophagy does not protect cells undergoing necrosis or apoptosis upon glucose deprivation. Moreover, glucose deprivation did not induce autophagic flux in any of the four cell lines analyzed, even though mTOR was inhibited. Indeed, glucose deprivation inhibited basal autophagic flux. In contrast, the glycolytic inhibitor 2-deoxyglucose induced prosurvival autophagy. Further analyses indicated that in the absence of glucose, autophagic flux induced by other stimuli is inhibited. These data suggest that the role of autophagy in response to nutrient starvation should be reconsidered.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ryan, Professor Kevin
Authors: Ramirez-Peinado, S., Leon-Annicchiarico, C. L., Galindo-Moreno, J., Iurlaro, R., Caro-Maldonado, A., Prehn, J. H.M., Ryan, K. M., and Munoz-Pinedo, C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Journal of Biological Chemistry
Journal Abbr.:J Biol Chem.
Publisher:American Society for Biochemistry and Molecular Biology, Inc.
ISSN:0021-9258
ISSN (Online):1083-351X

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