Lysosome-vacuolar apparatus

CONTROL OF METABOLIC HYDROLYSIS IN THE LYSOSOME-VACUOLAR APPARATUS... 

The main purpose of this review is the identification and definition of the lysosome-vacuolar apparatus as it pertains to the control and regulation of intracellular metabolic hydrolysis. No attempt is made to review work devoted to the isolation, characterization or morphology of the lysosome-vacuolar system in mammalian cells. The reader is referred to earlier reviews (de Duve, 1963, 1968 NovikofiF, 1963 de Duve and Wat-tiaux, 1966 Verity, 1965) for detailed considerations of histochemistry, biogenesis, drug-lysosome interaction and pathological aspects pertaining to the lysosome concept. 

This review will define a simplified schematic model of the lysosome-vacuolar apparatus which will provide a framework for subsequent discussion on the control and modulation of metabolic hydrolysis. 

Of paramount importance to our subsequent discussion on the role, regulation and control of metabolic hydrolysis is an understanding of the morphological and biochemical substrate underlying the concept of the lysosomal-vacuolar apparatus. Central to this theme is the presence of an intracellular membrane-bound vacuolar system. The biochemically and morphologically defined entities of the lysosomal-vacuolar apparatusi... 

Fig. 1. Model schema of the lysosome-vacuolar apparatus in mammalian cells. The Integrated components of the membrane structured apparatus are presented as existing in dynamic equilibrium. Acid hydrolases, produced (phase 1) in the endoplasmic reticulum, are channeled and packaged in the Golgi system (phase of vesiculatlon, phase 2). The subsequent translocation of acid hydrolases or secretory product is dependent upon the metabolic state of the cell, need for segregated catabolic activity of macromolecules (phase 3), or endocytic-exocytic activity.

The above brief comments on the model of the lysosome-vacuolar apparatus help define the horizons for subsequent discussion. This discussion is centered on the problem of control of hydrolytic activity by the lysosome-vacuolar system. Examination of the model brings into focus the major elements which may be involved in controlling intracellular degra-dative activity, itself poised upon the normal functioning of the lysosome-vacuolar system. We may state here that control of acid hydrolase... 

Acid hydrolase-membrane interaction and maintenance of optimal microenvironment in lysosome-vacuolar apparatus, for hydrolytic metabolism... 

For clarity in discussion, the control and modulating factors acting on the lysosome-vacuolar apparatus will be discussed in separate contexts, but we must stress the interdependence and cohesion of the individual parameters. 

The catabolic activities of the acid hydrolases occur either extracellu-larly through the process of exocytosis or intracellularly. Here we shall consider control of the catabolic hydrolysis occurring through activity of intravacuolar add hydrolases. Figure 1 diagrams the membrane system associated with the lysosomal-vacuolar apparatus and its catabolic activity and portrays the central role of the membrane-sequestered digestive vacuole. Biochemical studies of the lysosome-vacuolar system have al-... 

The role of the lysosome-vacuolar apparatus in controlling and modifying acid hydrolytic and catabolic activity in an intracellular environment may be examined as three interdependent parameters (A) control... 

Any detailed discussion of these individual phases must be speculative, but is valuable because of the critical importance of membrane fusion in the control of acid hydrolase activity in the lysosome-vacuolar apparatus. 

Acid hydrolase activity is poised for optimal activity and control by the nature of the enzyme microenvironment within the lysosome-vacuolar apparatus. A significant feature of this control has already been discussed in Section VI A.l. It was demonstrated that an interposed membrane precluded normal access of substrate to active site. In this section we will consider those factors which allow for optimal hydrolase activity within the compartmentalized vacuolar system. It must be realized that the lysosome-vacuolar system is maintained in a dynamic state and that trans-membrane diffusion of intermediates and metabolites may be oc-... 

The limitation of add hydrolase activity is of paramount importance to the normal functional behavior of the lysosome-vacuolar apparatus. We have previously considered the part played by pH, membrane segrega-... 

Straus and Oliver (1955) provided the first indication of ffie relationship between the association of an injected foreign protein and add hydrolases within the kidney cell Further work defined the nature of the endocytic phenomenon and helped consolidate our knowledge on the nature of the phagosome-lysosome interaction with subsequent formation of a digestive vacuole (for references, see Trump, 1961 Maunsbach, 1966a,b Straus, 1964). While the process and end result of endocytosis will stimulate the lysosome-vacuolar apparatus (see Section HI R and Fig. 3), studies on the nature, mechanism, and control of endocytosis are not warranted in this review (Brandt and Freeman, 1967, discuss the value of surface chemistry in pinocytosis). There is no doubt that the interrelationships between the endocytic vacuole and various compartments of ffie lysosome-vacuolar apparatus in situ, are of great importance. Some aspects of these relations have been discussed throughout this review. 

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