Figure 1.
Regulation of autophagy by ceramide. Ceramide (Cer) impinges both on the signaling pathway of autophagy and on the molecular machinery involved in the early steps of autophagosome formation such as the Beclin 1 complex. Ceramide regulates autophagy signaling by inhibiting Akt/PKB and the entry of nutrients. The low intracellular concentration of nutrients mimics decreases in the activity of the mTORC1 complex (not shown in the figure). Alternatively the low intracellular concentration of amino acids (AA) induced by ceramide may activate JNK1. Like starvation, ceramide favors the phosphorylation of Bcl-2 and its dissociation from Beclin 1 (Boxed P). Ceramide induces the expression of the BH3-only protein BNIP3, which competes with the BH3 domain of Beclin 1 to dissociate the Beclin 1:Bcl-2 complex (Boxed BH3). Finally, JNK1/2 activates the transcription factor c-Jun, leading to the upregulation of Beclin 1, and the stimulation of autophagy.