Figure 6.

Summary model. (A) Phenotypic homology of terminally differentiated autophagy-deficient keratinocytes, sebocytes, and HaGl cells. In all cell types, the aggregation of ribosomes and accumulation of lysosomes is observed upon ablation of autophagy. In keratinocytes, these aggregates occur at keratohyalin fibres and cause only a very mild phenotype. In the lipid producing SGl and HaGl, additionally, lipids are incorporated into an RB. A unique feature for the HaGl cells are the observed lamellar stacks of smooth ER, which form pseudo-crystalline structures. (B) Model for the dual role of autophagy in cells of the epithelial lineage. On the one hand in basal cells autophagy is required to maintain cell viability by eliminating toxic metabolic by-products. On the other hand, during terminal differentiation when cells have become increasingly resistant to apoptosis, autophagy controls cell death. In this type II cell death (CDA), the trans-Golgi expands and produced an excess of lysosomes. During CDA, autophagosomes target cellular constituents and degrade them by the fusion with lysosomes. Through the perforation of the cell membranes, either a homogenous sebum or flattened corneocytes are generated, respectively, in the glands or the skin. When autophagy is blocked, lysosomes accumulate and together with cellular remnants form aggregates (RB). Ultimately, cell death is delayed and cells remain incompletely degraded.