Steps in the autophagy pathway.
Autophagy is a process by which cytoplasmic contents are sequestered by autophagosomes and degraded upon fusion with lysosomes. Autophagy occurs at a basal level and is regulated by several pathways. Once autophagy is induced, an isolation membrane is formed by vesicle nucleation. Beclin 1 interacts with the Vps34 protein complex and is involved in this initial step by increasing the activity of Vps34 (a type of PI3K). Therefore, beclin 1 is a positive regulator of the autophagy pathway and promotes its induction. PE is conjugated to cytosolic LC3-I and converts it into lipidated LC3-II. LC3-II localizes to both the outside and the inside membranes of autophagosomes and therefore is often used as a marker. After their formation, autophagosomes mature through fusion with endosomal compartments and with lysosomes to form autolysosomes for degradation of cytosolic components. In the endosomal/lysosomal pathway, mono-ubiquitination serves as a signal for targeting transmembrane cargo in early endosomes to multivesicular bodies. Aβ can be generated in multivesicular bodies and autophagosomes. The study by Pickford et al. in this issue of the
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