title: Glucose-starved cells do not engage in prosurvival autophagy.
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.
authors.affiliation: From the Cell Death Regulation Group, IDIBELL (Bellvitge Biomedical Research Institute), L'Hospitalet de Llobregat, Barcelona, 08908 Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Ramírez-Peinado
authors.affiliation: From the Cell Death Regulation Group, IDIBELL (Bellvitge Biomedical Research Institute), L'Hospitalet de Llobregat, Barcelona, 08908 Spain.
authors.forename: Clara Lucía
authors.initials: CL
authors.lastname: León-Annicchiarico
authors.affiliation: From the Cell Death Regulation Group, IDIBELL (Bellvitge Biomedical Research Institute), L'Hospitalet de Llobregat, Barcelona, 08908 Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Galindo-Moreno
authors.affiliation: From the Cell Death Regulation Group, IDIBELL (Bellvitge Biomedical Research Institute), L'Hospitalet de Llobregat, Barcelona, 08908 Spain.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Iurlaro
authors.affiliation: From the Cell Death Regulation Group, IDIBELL (Bellvitge Biomedical Research Institute), L'Hospitalet de Llobregat, Barcelona, 08908 Spain.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Caro-Maldonado
authors.affiliation: the Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland, and.
authors.forename: Jochen H M
authors.initials: JHM
authors.lastname: Prehn
authors.affiliation: Tumour Cell Death Laboratory, Cancer Research UK Beatson Institute, Glasgow G61 1BD, Scotland, United Kingdom.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Ryan
authors.affiliation: From the Cell Death Regulation Group, IDIBELL (Bellvitge Biomedical Research Institute), L'Hospitalet de Llobregat, Barcelona, 08908 Spain,. Electronic address: cmunoz@idibell.cat.
authors.forename: Cristina
authors.initials: C
authors.lastname: Muñoz-Pinedo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D000071193:Autophagy-Related Protein 7; D000071183:Autophagy-Related Proteins; D000071186:Beclin-1; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D003847:Deoxyglucose / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D000071456:Sequestosome-1 Protein; D013549:Sweetening Agents / Q000378:metabolism / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D051758:Transcription Factor TFIIH; D014157:Transcription Factors / Q000378:metabolism; D044764:Ubiquitin-Activating Enzymes / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000963:Antimetabolites; D051017:Apoptosis Regulatory Proteins; C502661:Atg7 protein, mouse; D000071183:Autophagy-Related Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; C115010:Becn1 protein, mouse; C490981:Gtf2h1 protein, mouse; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D013549:Sweetening Agents; D014157:Transcription Factors; D051758:Transcription Factor TFIIH; C025946:3-methyladenine; D003847:Deoxyglucose; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; C507524:ATG4B protein, human; C582881:Atg4b protein, mouse; D003546:Cysteine Endopeptidases; C509349:ATG7 protein, human; D000071193:Autophagy-Related Protein 7; D044764:Ubiquitin-Activating Enzymes; D005947:Glucose; D000225:Adenine
keywords: Apoptosis; Autophagy; Glucose; Necrosis (Necrotic Death); mTOR