Non-canonical autophagy: an exception or an underestimated form of autophagy?

Autophagy. 2008 Nov;4(8):1083-5. doi: 10.4161/auto.7068. Epub 2008 Nov 23.

Abstract

Macroautophagy (hereafter called autophagy) is a dynamic and evolutionarily conserved process used to sequester and degrade cytoplasm and entire organelles in a sequestering vesicle with a double membrane, known as the autophagosome, which ultimately fuses with a lysosome to degrade its autophagic cargo. Recently, we have unraveled two distinct forms of autophagy in cancer cells, which we term canonical and non-canonical autophagy. In contrast to classical or canonical autophagy, non-canonical autophagy is a process that does not require the entire set of autophagy-related (Atg) proteins in particular Beclin 1, to form the autophagosome. Non-canonical autophagy is therefore not blocked by the knockdown of Beclin 1 or of its binding partner hVps34. Moreover overexpression of Bcl-2, which is known to block canonical starvation-induced autophagy by binding to Beclin 1, is unable to reverse the non-canonical autophagy triggered by the polyphenol resveratrol in the breast cancer MCF-7 cell line. In MCF-7 cells, at least, non-canonical autophagy is involved in the caspase-independent cell death induced by resveratrol.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Autophagy* / genetics
  • Beclin-1
  • Cell Line, Tumor
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Resveratrol
  • Stilbenes / pharmacology

Substances

  • Antineoplastic Agents, Phytogenic
  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • Membrane Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Stilbenes
  • Phosphatidylinositol 3-Kinases
  • Resveratrol