Autophagosome formation--the role of ULK1 and Beclin1-PI3KC3 complexes in setting the stage.
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...The class III Vps34 lipid kinase, part of the Beclin1 complex, is then activated (Wirth et al., 2013), translocates to ER sites, and produces a pool of phosphatidylinositol 3-phosphate (PtdIns(3)P)....
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...For starvation-induced autophagy, it is also necessary to unleash negative regulators of the Beclin 1-VPS34 initiation complex, such as Bcl-2/Bcl-xL (Wirth et al., 2013)....
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...Similarly, deprivation from growth factors and/or amino acids leads to the inhibition of TORC1, which, when active, represses conventional autophagy....
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...The lower affinity of antiapoptotic proteins for the BH3 domain of Beclin 1—versus those for the BH3 domains of proapoptotic proteins—may account for the early activation of autophagy in response to stress (which involves disruption of Bcl-2/Bcl-xLBeclin 1 binding) which, if unsuccessful in keeping the cell alive, ultimately results in the cell’s transition to a proapoptotic state (which, as noted above, involves the release of proapoptotic molecules such as Bax and Bak) (Sinha and Levine, 2008)....
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...This preinitiation complex is, in turn, activated by AMPK and inhibited by TORC1 (Wirth et al., 2013), and as we have discussed, starvation conditions result in AMPK activation and TORC1 inhibition....
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...As a result of AMPK induction and/or TORC1 inhibition, autophagy is engaged, although other signals may bypass AMPK and TORC1 to engage autophagy (Figure 1)....
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