Figure 1

Healthy neurons execute highly efficient autophagy. (a) Autophagy induction begins with phagophore formation, which requires LC3 and Atg proteins. (b) As induction proceeds, the phagophore membrane elongates while continuing to recruit cytosolic proteins and organelles. As the phaogphore membrane closes, Atg proteins dissociate. The final encapsulated vacuole is now called an autophagosome. (c) Autophagosomes fuse with lysosomes, and LC3 proteins dissociate from the membrane. (d) The resulting autolysosome contains active acidic hyrdolases that degrade enclosed cytosolic content. Neurons contain more abundant cathepsin-positive autolysosomes. (e) Autophagy completion is marked by digestion of the autophagosome and autophagosomal content and the release of amino acids and other metabolic products. APP, amyloid precursor protein; LC3, autophagosome-bound phosphatidylethanolamine-conjugated microtubule-associated protein light chain 3; PS1, presenilin 1.