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. 2019 Aug 6;63(3):297–312. doi: 10.1042/EBC20180071

Figure 1. Overview of disease mechanisms caused by mutations in BM collagens.

Figure 1

Collagen IV (COL4, black arrows) proteins harbouring nonsense mutations are processed in the ER, resulting in reduced secretion of proteins that are incorporated in the ECM, causing matrix defects (indicated by holes). Missense mutations in collagen IV and VII (COL7) can result in their ER retention and ER stress, and subsequent reduction in secretion (dashed arrows). COL4A5 mutations can also induce autophagy. Mutant collagen IV may also be incorporated in the ECM, resulting in BM defects. Nonsense mutations in collagen VI (COL6), VII (COL7), XVII (COL17), XV (COL15) and XVIII (COL18) (solid arrows) do not result in ER retention but rather in reduced incorporation in the ECM (yellow dashed arrow). Matrix defects resulting from COL6 mutations (light green) lead to failure to induce autophagy (via an as yet unknown mechanism) and result in mitochondrial defects and production of reactive oxygen species (ROS). Matrix defects, resulting from COL15 deficiency (brown arrow) also cause mitochondrial defects and ROS production.