Mitochondrial dysfunction in CD47-mediated caspase-independent cell death: ROS production in the absence of cytochrome c and AIF release.

Abstract:

:Ligation of CD47 by its natural ligand thrombospondin (TSP), or cross-linking by CD47 antibodies, triggers caspase-independent cell death in normal and leukemic cells. This kind of cell death is characterised by the cytoplasmic events of apoptosis including externalisation of phosphatidylserines and mitochondria swelling. We report herein selective mitochondrial changes in CD47-dependent cell death of T cells. After T cell stimulation via CD47, a rapid mitochondrial transmembrane potential (deltapsi(m)) disruption is accompanied by the production of reactive oxygen species (ROS) and phosphatidylserine exposure. Surprisingly, mitochondrial dysfunction does not induce cytochrome c or AIF release. Moreover, the dying cells do not exhibit caspase-3 activation and display intact nuclei without any large-scale, or oligonucleosomal DNA fragmentation. We conclude that DeltaPsi(m) loss and ROS production are an early step in CD47-dependent killing and neither cytochrome c, nor AIF are implicated in this new cell death pathway.

journal_name

Biochimie

journal_title

Biochimie

authors

Roué G,Bitton N,Yuste VJ,Montange T,Rubio M,Dessauge F,Delettre C,Merle-Béral H,Sarfati M,Susin SA

doi

10.1016/s0300-9084(03)00129-9

keywords:

subject

Has Abstract

pub_date

2003-08-01 00:00:00

pages

741-6

issue

8

eissn

0300-9084

issn

1638-6183

pii

S0300908403001299

journal_volume

85

pub_type

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