FIG. 12.

The accumulation of “waste” is a consequence of imperfect autophagy. Lysosomal enzymes are produced in the trans-Golgi network (TGN) and by secretory vesicles transported to late endosomes that acidify and maturate into lysosomes (see Fig. 7), which in turn fuse with autophagosomes (APSs). The continual fusion and fission of the lysosomal vacuoles ensures the distribution of acid hydrolases within the lysosomal compartment, including APS. In contrast to a young cell (A) that has only few lysosomes containing the undegradable age-pigment lipofuscin (Lf), senescent postmitotic cells (B) contain large numbers of Lf-containing lysosomes, to which more and more lysosomal enzymes are directed in a useless effort to degrade lipofuscin. These lysosomal enzymes are lost for useful purposes (e.g., for the degradation of newly autophagocytosed material), resulting in a delayed turnover and the accumulation of waste products. Damaged/dysfunctional mitochondria are indicated by dark shading.