FIGURE 7:
The role of keratins in colon energy metabolism. The SCFA butyrate is the primary source of energy for colonic epithelium and is involved in the maintenance of epithelial homeostasis. Butyrate and other SCFAs are produced by the colonic microflora via fermentation of, for example, dietary fiber. The amount of luminal bacteria is slightly decreased (Habtezion et al., 2011) and while the ratio of butyrate-producing species is unaltered, butyrate levels are increased in K8−/− compared with K8+/+ colonic lumen. SCFAs are absorbed primarily by MCT1, which is down-regulated in K8−/− colon. No evidence of MCT1 mistargeting as a consequence of K8-down-regulation could be detected. The localization of MCT1 in the cell varies depending on the nutritional state of the colon and changes from a lateral to a presumably functional apical location. SCFAs are transported to mitochondria, where they are converted to acetyl-CoA through β-oxidation. Acetyl-CoA is then used in the citric acid cycle and for ketone body production, which serves as energy in colonocytes under normal conditions. The absence of keratin filaments leads to decreased energy metabolism in the colon of K8−/− mice, which may be central in the observed K8−/− colitis phenotype.