The autophagosomal-lysosomal compartment in programmed cell death.

In the last decade a tremendous progress has been achieved in understanding the control of apoptosis by survival and death factors as well as the molecular mechanisms of preparation and execution of the cell's suicide. However, accumulating evidence suggests that programmed cell death (PCD) is not confined to apoptosis but that cells use different pathways for active self-destruction as reflected by different morphology: condensation prominent, type I or apoptosis; autophagy prominent, type II; etc. Autophagic PCD appears to be a phylogenetically old phenomenon, it may occur in physiological and disease states. Recently, distinct biochemical and molecular features have been be assigned to this type of PCD. However, autophagic and apoptotic PCD should not be considered as mutually exclusive phenomena. Rather, they appear to reflect a high degree of flexibility in a cell's response to changes of environmental conditions, both physiological or pathological. Furthermore, recent data suggest that diverse or relatively unspecific signals such as photodamage or lysosomotropic agents may be mediated by lysosomal cysteine proteases (cathepsins) to caspases and thus, apoptosis. The present paper reviews morphological, functional and biochemical/molecular data suggesting the participation of the autophagosomal-lysosomal compartment in programmed cell death.