Regulation of autophagy by stress-responsive transcription factors

Federico Pietrocola, Valentina Izzo, Mireia Niso-Santano, Erika Vacchelli, Lorenzo Galluzzi, Maria Chiara Maiuri, Guido Kroemer

Research output: Contribution to journalReview articlepeer-review

220 Scopus citations

Abstract

Autophagy is an evolutionarily conserved process that promotes the lysosomal degradation of intracellular components including organelles and portions of the cytoplasm. Besides operating as a quality control mechanism in steady-state conditions, autophagy is upregulated in response to a variety of homeostatic perturbations. In this setting, autophagy mediates prominent cytoprotective effects as it sustains energetic homeostasis and contributes to the removal of cytotoxic stimuli, thus orchestrating a cell-wide, multipronged adaptive response to stress. In line with the critical role of autophagy in health and disease, defects in the autophagic machinery as well as in autophagy-regulatory signaling pathways have been associated with multiple human pathologies, including neurodegenerative disorders, autoimmune conditions and cancer. Accumulating evidence indicates that the autophagic response to stress may proceed in two phases. Thus, a rapid increase in the autophagic flux, which occurs within minutes or hours of exposure to stressful conditions and is entirely mediated by post-translational protein modifications, is generally followed by a delayed and protracted autophagic response that relies on the activation of specific transcriptional programs. Stress-responsive transcription factors including p53, NF-κB and STAT3 have recently been shown to play a major role in the regulation of both these phases of the autophagic response. Here, we will discuss the molecular mechanisms whereby autophagy is orchestrated by stress-responsive transcription factors.

Original languageEnglish
Pages (from-to)310-322
Number of pages13
JournalSeminars in Cancer Biology
Volume23
Issue number5
DOIs
StatePublished - Oct 2013
Externally publishedYes

Keywords

  • AMPK
  • Beclin 1
  • Cancer
  • Mitophagy
  • MTOR
  • PKR

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