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Publication : Unsaturated fatty acids induce non-canonical autophagy.

First Author  Niso-Santano M Year  2015
Journal  EMBO J Volume  34
Issue  8 Pages  1025-41
PubMed ID  25586377 Mgi Jnum  J:220595
Mgi Id  MGI:5635719 Doi  10.15252/embj.201489363
Citation  Niso-Santano M, et al. (2015) Unsaturated fatty acids induce non-canonical autophagy. EMBO J 34(8):1025-41
abstractText  To obtain mechanistic insights into the cross talk between lipolysis and autophagy, two key metabolic responses to starvation, we screened the autophagy-inducing potential of a panel of fatty acids in human cancer cells. Both saturated and unsaturated fatty acids such as palmitate and oleate, respectively, triggered autophagy, but the underlying molecular mechanisms differed. Oleate, but not palmitate, stimulated an autophagic response that required an intact Golgi apparatus. Conversely, autophagy triggered by palmitate, but not oleate, required AMPK, PKR and JNK1 and involved the activation of the BECN1/PIK3C3 lipid kinase complex. Accordingly, the downregulation of BECN1 and PIK3C3 abolished palmitate-induced, but not oleate-induced, autophagy in human cancer cells. Moreover, Becn1(+/-) mice as well as yeast cells and nematodes lacking the ortholog of human BECN1 mounted an autophagic response to oleate, but not palmitate. Thus, unsaturated fatty acids induce a non-canonical, phylogenetically conserved, autophagic response that in mammalian cells relies on the Golgi apparatus.
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