Fig. 1.Classical autophagy signaling pathway. Classical autophagy
regulation pathways include mTOR-dependent and mTOR-independent. mTOR is a key
molecule in autophagy signal, which inhibits autophagy by phosphorylating
downstream p70S6K1, UVRAG and ULK. PI3K/Akt upstream of mTOR can activate mTOR by
preventing the formation of TSC1/2 complex. Changes in energy status can activate
AMPK, and activated AMPK phosphorylates RAPTOR to inactivate mTOR. Moreover, AMPK
and JNK-1 are able to promote the dissociation of Beclin1 and Bcl2-2 by
phosphorylation, thus promoting the formation of autophagy complex. Finally,
Ca and cAMP activate PLC- and Rap2B via the EPAC pathway, and
ultimately inhibit autophagy.