Role of JNK1-dependent Bcl-2 phosphorylation in ceramide-induced macroautophagy

Sophie Pattingre, Chantal Bauvy, Stéphane Carpentier, Thierry Levade, Beth Levine, Patrice Codogno

Research output: Contribution to journalArticlepeer-review

237 Scopus citations


Macroautophagy is a vacuolar lysosomal catabolic pathway that is stimulated during periods of nutrient starvation to preserve cell integrity. Ceramide is a bioactive sphingolipid associated with a large range of cell processes. Here we show that short-chain ceramides (C2-ceramide and C 6-ceramide) and stimulation of the de novo ceramide synthesis by tamoxifen induce the dissociation of the complex formed between the autophagy protein Beclin 1 and the anti-apoptotic protein Bcl-2. This dissociation is required for macroautophagy to be induced either in response to ceramide or to starvation. Three potential phosphorylation sites, Thr69, Ser 70, and Ser87, located in the non-structural N-terminal loop of Bcl-2, play major roles in the dissociation of Bcl-2 from Beclin 1. We further show that activation of c-Jun N-terminal protein kinase 1 by ceramide is required both to phosphorylate Bcl-2 and to stimulate macroautophagy. These findings reveal a new aspect of sphingolipid signaling in up-regulating a major cell process involved in cell adaptation to stress.

Original languageEnglish (US)
Pages (from-to)2719-2728
Number of pages10
JournalJournal of Biological Chemistry
Issue number5
StatePublished - Jan 30 2009

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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