Making autophagosomes: Localized synthesis of phosphatidylinositol 3-phosphate holds the clue

• Published in: Autophagy 2008-11, Vol.4 (8), p.1093-1096
• Main Authors: Walker, Simon, Chandra, Priya, Manifava, Maria, Axe, Elizabeth, Ktistakis, Nicholas T.
• Format: Article
• Language: English
• Subjects: Amino Acids - metabolism; Autophagy; Binding; Biology; Bioscience; Calcium; Cancer; Cell; Cell Membrane - metabolism; Cycle; Endoplasmic Reticulum - metabolism; Humans; Landes; Organogenesis; Phagosomes - metabolism; Phosphatidylinositol Phosphates - biosynthesis; Proteins; Proteins - metabolism
• ISSN: 1554-8627; 1554-8635
• DOI: 10.4161/auto.7141

Autophagy presents a topological challenge for the cell because it requires delivery of cytosolic material to the lumen of a membrane bound compartment, the lysosome. This is solved in an ingenious way by the formation of a double-membrane vesicle, the autophagosome, which captures cytosolic proteins and organelles during its transformation from a planar membrane disk into a sphere. In this way, cytosolic material first becomes lumenal and is then delivered for degradation to the lysosome. An unsolved set of questions in autophagy concerns the membrane of the autophagosome: what are the signals for its formation and what is its identity? Recently we provided some clues that may help answer these questions. 1 By following the dynamics of several phosphatidylinositol 3-phosphate (PI3P)-binding proteins during amino acid starvation (and autophagy induction) we concluded that at least some autophagosomes are formed in a starvation-induced, PI3P-enriched membrane compartment dynamically connected to the endoplasmic reticulum (ER). We termed the membranes of this compartment omegasomes (from their omega-like shape). Our data suggest that PI3P is important for providing localization clues and perhaps for facilitating the fusion step at the final stage of autophagosome formation. Addendum to: Axe EL, Walker SA, Manifava M, Chandra P, Roderick HL, Habermann A, et al. Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum. J Cell Biol 2008; 182:685-701.