Non-canonical autophagy: an exception or an underestimated form of autophagy?
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.
Laboratory of Cellular and Molecular Endocrinology, Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy. francesca.scarlatti@unito.it
Francesca
F
Scarlatti
Roberta
R
Maffei
Isabelle
I
Beau
Riccardo
R
Ghidoni
Patrice
P
Codogno
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000235:genetics; D000071186:Beclin-1; D045744:Cell Line, Tumor; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D013267:Stilbenes; D019869:Phosphatidylinositol 3-Kinases; D000077185:Resveratrol