The nascent polypeptide-associated complex is essential for autophagic flux.

The ribosome-associated nascent polypeptide-associated complex (NAC) is involved in multiple cotranslational processes, including protein transport into the ER and mitochondria, and also acts as a chaperone to assist protein folding. Here we demonstrated that NAC is also essential for autophagic degradation of a variety of protein aggregates in C. elegans. Loss of function of NAC impairs lysosome function, resulting in accumulation of autophagic substrates in enlarged autolysosomes. Knockdown of mammalian NAC also causes accumulation of nondegradative autolysosomes. Our study revealed that NAC plays an evolutionarily conserved role in the autophagy pathway and thus in maintaining protein homeostasis under physiological conditions.