LYSOSOMAL MEMBRANE PERMEABILIZATION AS APOPTOGENIC FACTOR
A. B. Pupyshev
Novosibirsk State Medical University;
e-mail: apupyshev@mail.ru
Lysosomal membrane labilizing agents (incl. proapoptotic proteins of Bcl-2 family, LAPF, p53), estimation of lysosomal membrane permeabilization in living cells, the new data on
differential permeabilization of lysosomal membranes, membrane stabilizing factors (incl. Hsp70), relations between lysosomal membrane damage, and initiation of apoptosis were considered.
Signal effect of lysosomal membrane permeabilization is caused preferentially by release of cathepsin B and D in cytosol. Subsequent numerous pathways of apoptogenic signa-lization include
proteolytic attack/activation on signal cytosolic proteins, mitochondria, procaspases, cell nuclei. The mainstream of the cell damage is connected with activation pf proapoptotic Bid and Bax,
leading to permeabilization of the outer mitochondrial membrane, release of cytochrome c into cytosol and activation of caspase cascade. Translocation of the lysosoma enzymes in cytosol is
capable to induce both the caspase-dependent and caspase-independent paths of apoptosis.
Key words: apoptosis, cathepsin B, cathepsin D, lysosomal membrane permeabilization, lysosomes, necrosis
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