Granzyme B-mediated Cytochrome C Release is Regulated by the Bcl-2 Family Members Bid and Bax

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2000 Nov 21

PMID 11085742

Citations 76

Authors

J A Heibein

I S Goping

M Barry

M J Pinkoski

G C Shore

D R Green

R C Bleackley

Affiliations

Soon will be listed here.

Abstract

Cytotoxic T lymphocytes (CTLs) destroy target cells through a mechanism involving the exocytosis of cytolytic granule components including granzyme B (grB) and perforin, which have been shown to induce apoptosis through caspase activation. However, grB has also been linked with caspase-independent disruption of mitochondrial function. We show here that cytochrome c release requires the direct proteolytic cleavage of Bid by grB to generate a 14-kD grB-truncated product (gtBid) that translocates to mitochondria. In turn, gtBid recruits Bax to mitochondria through a caspase-independent mechanism where it becomes integrated into the membrane and induces cytochrome c release. Our results provide evidence for a new pathway by which CTLs inflict damage and explain the caspase-independent mechanism of mitochondrial dysfunction.

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