Fig. 5.

Model for how NMD regulates autophagy and amino-acid availability. The PERK arm of the UPR, as well as other cues, including Rapamycin, can trigger autophagy in cells via induction of ATF4, a transcription factor that, in turn, drives the expression of another transcription factor, CHOP. CHOP activates transcription of genes encoding essential autophagy factors, including those shown in the figure. ATF4 and CHOP are both encoded by NMD target mRNAs, providing a molecular basis for how high NMD activity represses autophagy. Since amino acids are recycled by autophagy, one downstream consequence of this regulation is altered amino-acid availability. NMD also impacts amino-acid availability by repressing the expression of the cystine-glutamate transporter xCT. NMD targets SLC7A11 mRNA, which encodes one of the subunits of this amino-acid transporter