LC3-I conversion to LC3-II does not necessarily result in complete autophagy

Int J Mol Med. 2008 Dec;22(6):781-5.

Abstract

Autophagy was induced in human neuroblastoma SH-SY5Y cells by two different procedures: deprivation of fetal serum in culture medium, or treatment with dopamine. 3-methyladenine prevented autophagy in the two procedures. Although it is usually considered that the conversion of soluble LC3-I to lipid bound LC3-II is associated with the formation of autophagosomes, the inhibition of autophagy with 3-methyladenine prevented this transformation in serum-deprived but not in dopamine-treated cells. While the PI3K-mTOR pathway was inhibited by serum deprivation, dopamine increased the phosphorylation of Akt but inhibited mTOR activity in a similar way to rapamycin. Dopamine and rapamycin increased LC3-II levels by a mechanism not prevented by 3-methyladenine. The activation of LC3-I to LC3-II may then be necessary but not sufficient to trigger cell autophagy. Thus, the increase in LC3-II, as the main biochemical parameter for autophagy at present, should be considered with caution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / pharmacology
  • Autophagy* / drug effects
  • Blotting, Western
  • Dopamine / pharmacology
  • Humans
  • Microscopy, Electron
  • Microscopy, Fluorescence
  • Microtubule-Associated Proteins / metabolism*
  • Neuroblastoma
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Kinases / metabolism
  • Serum
  • Sirolimus / pharmacology
  • TOR Serine-Threonine Kinases
  • Tumor Cells, Cultured

Substances

  • MAP1LC3A protein, human
  • Microtubule-Associated Proteins
  • 3-methyladenine
  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Adenine
  • Dopamine
  • Sirolimus