Background
Activating molecule in Beclin1-regulated autophagy is a WD40-containing protein expressed during neurodevelopment that is required for neural tube development and autophagy. Several studies have identified interactions between Ambra1 with regulators of autophagy and apoptosis. Ambra1 was originally found to interact with Beclin-1, a key protein responsible for activating the class III PI3K Vps34. Further studies showed that Ambra1 tethers the Beclin-1-Vps34 complex to the cytoskeletal network through dynein light chains and that during autophagy ULK1 phosphorylates Ambra1, resulting in disassociation with dynein and translocation of the Beclin-Vps34 complex to the endoplasmic reticulum to initiate autophagosome formation. In addition, it has been found that Ambra1 binds to mitochondrial Bcl-2 and that this interaction is regulated by either apoptosis or autophagy. Ambra1 also interacts with Parkin, an E3 ubiquitin ligase important for mitophagy, a selective autophagic process of mitochondrial clearance.
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