146 SUBCELLULAR PARTICLES 



processes in order to compete successfully with the hydrolytic splitting. This at 

 least is what has generally been found in vitro (see, for instance, 4, 64, 35 and 

 34). Admittedly, as is believed to be the case for some ATPases, the situation may 

 be different in an intact system. 



j) The location of the lysosomal enzymes does not correspond with the sites 

 of maximum synthesis, as evidenced by isotope experiments. 



Our working hypothesis will therefore be that lysosomes are involved in 

 processes of acid hydrolysis. These may comprise: digestion of foreign material, 

 engulfed by pinocytosis, athrocytosis or phagocytosis; physiological autolysis, as 

 presumably occurs to some extent in all tissues, and particularly as part of the 

 more specialized processes of involution, metamorphosis, holocrine secretion, etc.; 

 pathological autolysis or necrosis. 



The hypothesis may be qualified further by stating that the normal segregation 

 of the lysosomal hydrolases within little impermeable bags may play an essential 

 part in keeping the lytic processes localized and, therefore, in protecting the cell 

 against generalized autolysis. 



Intracellular Digestion and Engulfing Processes. In a previous publication 

 (29), the hypothesis was put forward that lysosomes may be concerned with 

 localized phenomena of acid digestion and attention was called to an old obser- 

 vation by Horning (52), who described the participation of mitochondria-like 

 bodies in the formation of digestive vacuoles in amoebae. After the provisional 

 morphological identification of lysosomes was presented (66), the suggestion was 

 made by Bennett (11) that the particles may represent segregated phagocytosed or 

 pinocytosed material and that the enzymes associated with the granules may have 

 a role in breaking down some of the contents of the bodies. Referring to the 

 'residual bodies' of spleen macrophages, Palade(72) has expressed a siniilar 

 opinion, assuming that they represent terminal apearances of phagocytic vacuoles 

 and that the dense granular material they contain is a metal-organic compound 

 ( hemosiderin. i^ ferritin?). The involvement in engulfing processes of fairly poly- 

 morphic bodies surrounded by a single membrane has been demonstrated by 

 Odor (69), Felix and Dalton {^^) and Harford, Hamlin and Parker (42). 



The best evidence linking lysosomes with pinocytosis and related phenomena 

 stems from the studies on kidney droplets. The relationship of these granules to 

 'athrocytosis' — a term which was actually invented to explain their origin — rests 

 on a long line of morphological studies (see 37, 74, 70, 71), and these have been 

 amply verified by the more recent biochemical in\estigations. Indications that the 

 droplets contain the injected material have been obtained by Oliver, MacDowell, 

 Moses and Lee (71) after the administration of proteins, and by Lee (61) and 

 Kretchmer and Cherot (55) after the injection of amino acids. The segregation of 

 egg white by the droplets was later demonstrated on purified fractions by Straus 

 and Oliver (96) with the aid of a semic]uantitati\c serological method. These 



