Figure 9.

A model for the degradation of misfolded procollagen molecules in the ER. Type I collagen trimers that contain the misfolded proα1(I) chain due to chaperone-disruption or genetic mutation accumulate as aggregates in the ER. These aggregates are eliminated by an autophagy–lysosome pathway, but not by ERAD. In contrast, mutant type I collagen proα1 chain that is deficient in trimer formation is eliminated by the ERAD pathway. In addition, misfolded protein (NHK) and misfolded procollagens are degraded independently by ERAD or autophagy, respectively, in the same cell. Red stars indicate mutated amino acids.