Autophagy eliminates a specific species of misfolded procollagen and plays a protective role in cell survival against ER stress.

Type I collagen is one of the most abundant proteins in the human body and is essential for tissue formation. Mutations in collagen cause severe abnormalities in bone formation, including osteogenesis imperfecta. Although the mutant collagens are retained in the endoplasmic reticulum (ER) and are toxic to the cell, little is known about how they are removed from the ER. Using two independent cell lines that produce misfolded collagens, we recently demonstrated that procollagen, which is misfolded and accumulated as trimers, is eliminated through the autophagy-lysosomal pathway, not through the ER-associated degradation (ERAD) pathway. In contrast, misfolded procollagen monomer is degraded via ERAD. Moreover, autophagic elimination and ERAD occur independently and exert protective roles and promote cell survival. Thus, autophagy and ERAD, in concert, contribute to eliminating toxic species of misfolded and accumulated proteins from the ER.