The IKK complex contributes to the induction of autophagy

Alfredo Criollo, Laura Senovilla, Hélène Authier, Maria Chiara Maiuri, Eugenia Morselli, Ilio Vitale, Oliver Kepp, Ezgi Tasdemir, Lorenzo Galluzzi, Shensi Shen, Maximilien Tailler, Nicolas Delahaye, Antoine Tesniere, Daniela De Stefano, Aména Ben Younes, Francis Harper, Gérard Pierron, Sergio Lavandero, Laurence Zitvogel, Alain IsraelVéronique Baud, Guido Kroemer

Research output: Contribution to journalArticle

Abstract

In response to stress, cells start transcriptional and transcription- independent programs that can lead to adaptation or death. Here, we show that multiple inducers of autophagy, including nutrient depletion, trigger the activation of the IKK (IB kinase) complex that is best known for its essential role in the activation of the transcription factor NF-B by stress. Constitutively active IKK subunits stimulated autophagy and transduced multiple signals that operate in starvation-induced autophagy, including the phosphorylation of AMPK and JNK1. Genetic inhibition of the nuclear translocation of NF-B or ablation of the p65/RelA NF-B subunit failed to suppress IKK-induced autophagy, indicating that IKK can promote the autophagic pathway in an NF-B-independent manner. In murine and human cells, knockout and/or knockdown of IKK subunits (but not that of p65) prevented the induction of autophagy in response to multiple stimuli. Moreover, the knockout of IKK-Β suppressed the activation of autophagy by food deprivation or rapamycin injections in vivo, in mice. Altogether, these results indicate that IKK has a cardinal role in the stimulation of autophagy by physiological and pharmacological stimuli.

Original languageEnglish
Pages (from-to)619-631
Number of pages13
JournalEMBO Journal
Volume29
Issue number3
DOIs
Publication statusPublished - Feb 2010

Keywords

  • B
  • Hypoxia
  • Mice
  • NF-kappa
  • Rapamycin
  • Starvation

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

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  • Cite this

    Criollo, A., Senovilla, L., Authier, H., Maiuri, M. C., Morselli, E., Vitale, I., Kepp, O., Tasdemir, E., Galluzzi, L., Shen, S., Tailler, M., Delahaye, N., Tesniere, A., De Stefano, D., Younes, A. B., Harper, F., Pierron, G., Lavandero, S., Zitvogel, L., ... Kroemer, G. (2010). The IKK complex contributes to the induction of autophagy. EMBO Journal, 29(3), 619-631. https://doi.org/10.1038/emboj.2009.364