G. Kudla et al., The destabilization of lipid membranes induced by the C-terminal fragment of caspase 8-cleaved bid is inhibited by the N-terminal fragment, J BIOL CHEM, 275(30), 2000, pp. 22713-22718
Bid is a proapoptotic, BH8-domain-only member of the Bcl-2 family. In Fas-i
nduced apoptosis, Bid is activated through cleavage by caspase 8 into a 15,
5-kDa C-terminal fragment (t(c)Bid) and a 6.5 kDa N-terminal fragment (t(n)
Bid). Following the cleavage, t(c)Bid translocates to the mitochondria and
promotes the release of cytochrome c into the cytosol by a mechanism that i
s not understood. Here we report that recombinant t(c)Bid can act as a memb
rane destabilizing agent, t(c)Bid induces destabilization and breaking of p
lanar lipid bilayers without appearance of ionic channels; its destabilizin
g activity is comparable with that of Bax and at least 30-fold higher than
that of full-length Bid. Consistently, t(c)Bid, but not full-length Bid, pe
rmeabilizes liposomes at physiological pH. The destabilizing effect of t(c)
Bid on liposomes and planar bilayers is independent of the BH3 domain. In c
ontrast, mutations in the BH3 domain impair t(c)Bid ability to induce cytoc
hrome c release from mitochondria. The permeabilizing effect of t(c)Bid on
planar bilayers, liposomes, and mitochondria can be inhibited by t(c)Bid. I
n conclusion, our results suggest a dual role for Bid: BH3-independent memb
rane destabilization and BH3-dependent interaction with other proteins. Mor
eover, the dissociation of Bid after cleavage by caspase 8 represents an ad
ditional step at which apoptosis may be regulated.