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  • Title: Granzyme B can cause mitochondrial depolarization and cell death in the absence of BID, BAX, and BAK.
    Author: Thomas DA, Scorrano L, Putcha GV, Korsmeyer SJ, Ley TJ.
    Journal: Proc Natl Acad Sci U S A; 2001 Dec 18; 98(26):14985-90. PubMed ID: 11752447.
    Abstract:
    Granzyme B (GzmB) is a serine protease that is used by activated cytotoxic T lymphocytes to induce target cell apoptosis. Although GzmB directly cleaves the Bcl2 family member BID on target cell entry, Bid-deficient (and Bax, Bak doubly deficient) cells are susceptible to GzmB-induced death, even though they fail to release cytochrome c from mitochondria. GzmB still induces mitochondrial depolarization in Bax, Bak double knockout cells without cytochrome c release or opening of the permeability transition pore. Because GzmB cannot directly cause depolarization of isolated mitochondria, novel intracellular factor(s) may be required for GzmB to depolarize mitochondria in situ. GzmB therefore utilizes two distinct mitochondrial pathways to amplify the proapoptotic signal that it delivers to target cells.
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