A lysosomal protease enters the death scene.

The definition of lysosomes as cellular “suicide bags” derives from DeDuve’s early work on fractionation and identification of cellular organelles. Since lysosomes contain degradative systems for proteins, carbohydrates, and lipids, it seemed natural that they should participate in cellular death and dismantling. But the last five years have seen a rapid advance in our understanding of the genetics and biochemistry of cell death, and it is apparent that a well conserved specific program exists in metazoans to execute superfluous or disobedient cells. This program is called apoptosis. Lysosomes or their constituents had not been considered to participate in this process under normal circumstances, and one cannot find discussion of these organelles or their constituents in the most recent series of eloquent reviews that cover the entire field of apoptosis (1–7). To be sure, there is evidence that lysosomal hydrolases participate in the unruly form of cell death known as necrosis and in the autophagic cell death found in neuronal populations (8). It is even evident that lysosomal rupture can trigger apoptosis under certain pathologic conditions (9), but to this point there has been little reason to believe that lysosomes participate in bona fide physiological apoptosis (Figure 1).