Autophagy is also regulated by the activity of PI3K complexes. Yeast contains a single PI3K, Vps34, which is present in two different tetrameric complexes that share 3 common subunits, Vps34, Vps15, and Atg6 [20] . Complex I is required for the induction of autophagy and through its fourth component, Atg14, associates to the autophagosomal membranes where the lipid kinase activity of Vps34 is essential for generating the phosphatidylinositol-3-phosphate (PI3P) that permits the recruitment of other Atg proteins [9, 21] (Figure 1 ). Complex II contains Vps38 as the fourth subunit and it is involved in endosomal trafficking and vacuole biogenesis [20] . There are three types of PI3K in mammals: class I, II, and III. The functions of class II PI3K remains largely unknown, but both classes I and III PI3Ks are involved in autophagy. While class I PI3K is principally implicated in the modulation of signalling cascades, class III PI3K complexes regulate organelle biogenesis and, like yeast, contain three common components: hVps34, p150 (Vps15 ortholog), and Beclin 1 (Atg6 ortholog). The counterparts of Atg14 and Vps38 are called Atg14L/Barkor and UVRAG, respectively [22] [23] [24] . The Atg14L-containing complex plays a central role in autophagy and functions very similarly as the yeast complex I by directing the class III PI3K complex I to the phagophore to produce PI3P and initiate the recruitment of the Atg machinery ( Figure 1 ). Atg14L is thought to be present on the ER irrespective of autophagy induction [25] . Upon starvation, Atg14L localizes to autophagosomal membranes [8] . Importantly, depletion of Atg14L reduces PI3P production, impairs the formation of autophagosomal precursor structures, and inhibits autophagy [8, 24, 26, 27] . The UVRAG-containing class III PI3K complex also regulates autophagy but it appears to act at the intersection between autophagy and the endosomal transport pathways. UVRAG initially associates with the BAR-domain protein Bif-1, which may regulate mAtg9 trafficking from the trans-Golgi network (TGN) [28, 29] . UVRAG then interacts with the class C Vps/HOPS protein complex, promoting the fusion of autophagosomes with late endosomes and/or lysosomes [30] . Finally, the UVRAG-containing class III protein complex binds to Rubicon, a late endosomal and lysosomal protein that suppresses autophagosome maturation by reducing hVps34 activity [26, 31] . Importantly, both the Atg14L-and UVRAG-containing complexes interact through Beclin 1 with Ambra1, which in turn tethers these protein complexes to the cytoskeleton via an interaction with dynein [32, 33] . Following the induction of autophagy, ULK1 phosphorylates Ambra1 thus releasing the class III PI3K complexes from dynein and their subsequent relocalization triggers autophagosome formation. Therefore, Ambra1 constitutes a direct regulatory link between the Atg1/ULK1 and the PI3K complexes [32] .