Dual role for CHOP in the crosstalk between autophagy and apoptosis to determine cell fate in response to amino acid deprivation.

CHOP encodes a ubiquitous transcription factor that is one of the most important components in the network of stress-inducible transcription. In particular, this factor is known to mediate cell death in response to stress. The focus of this work is to study its pivotal role in the control of cell viability according to the duration of a stress like amino acid starvation. We show that during the first 6h of starvation, CHOP upregulates a number of autophagy genes but is not involved in the first steps of the autophagic process. By contrast, when the amino acid starvation is prolonged (16-48h), we demonstrated that CHOP has a dual role in both inducing apoptosis and limiting autophagy through the transcriptional control of specific target genes. Overall, this study reveals a novel regulatory role for CHOP in the crosstalk between autophagy and apoptosis in response to stress.