title: Glucose induces autophagy under starvation conditions by a p38 MAPK-dependent pathway.
abstract: Autophagy is a natural process of 'self-eating' that occurs within cells and can be either pro-survival or can cause cell death. As a pro-survival mechanism, autophagy obtains energy by recycling cellular components such as macromolecules or organelles. In response to nutrient deprivation, e.g. depletion of amino acids or serum, autophagy is induced and most of these signals converge on the kinase mTOR (mammalian target of rapamycin). It is commonly accepted that glucose inhibits autophagy, since its deprivation from cells cultured in full medium induces autophagy by a mechanism involving AMPK (AMP-activated protein kinase), mTOR and Ulk1. However, we show in the present study that under starvation conditions addition of glucose produces the opposite effect. Specifically, the results of the present study demonstrate that the presence of glucose induces an increase in the levels of LC3 (microtubule-associated protein 1 light chain)-II, in the number and volume density of autophagic vacuoles and in protein degradation by autophagy. Addition of glucose also increases intracellular ATP, which is in turn necessary for the induction of autophagy because the glycolysis inhibitor oxamate inhibits it, and there is also a good correlation between LC3-II and ATP levels. Moreover, we also show that, surprisingly, the induction of autophagy by glucose is independent of AMPK and mTOR and mainly relies on p38 MAPK (mitogen-activated protein kinase).
authors.affiliation: Cell Biology Laboratory, Príncipe Felipe Research Centre, C/Eduardo Primo Yúfera 3, 46012 Valencia, Spain.
authors.forename: Jose Félix
authors.initials: JF
authors.lastname: Moruno-Manchón
authors.forename: Eva
authors.initials: E
authors.lastname: Pérez-Jiménez
authors.forename: Erwin
authors.initials: E
authors.lastname: Knecht
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D041681:NIH 3T3 Cells; D010588:Phagosomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D059748:Proteolysis / Q000187:drug effects; D034622:RNA Interference; D014617:Vacuoles / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D016895:Culture Media, Serum-Free; D008869:Microtubule-Associated Proteins; D000255:Adenosine Triphosphate; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose