[HTML][HTML] Bid, Bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane

T Kuwana, MR Mackey, G Perkins, MH Ellisman… - Cell, 2002 - cell.com
T Kuwana, MR Mackey, G Perkins, MH Ellisman, M Latterich, R Schneiter, DR Green
Cell, 2002cell.com
Bcl-2 family proteins regulate the release of proteins like cytochrome c from mitochondria
during apoptosis. We used cell-free systems and ultimately a vesicular reconstitution from
defined molecules to show that outer membrane permeabilization by Bcl-2 family proteins
requires neither the mitochondrial matrix, the inner membrane, nor other proteins. Bid, or its
BH3-domain peptide, activated monomeric Bax to produce membrane openings that
allowed the passage of very large (2 megadalton) dextran molecules, explaining the …
Abstract
Bcl-2 family proteins regulate the release of proteins like cytochrome c from mitochondria during apoptosis. We used cell-free systems and ultimately a vesicular reconstitution from defined molecules to show that outer membrane permeabilization by Bcl-2 family proteins requires neither the mitochondrial matrix, the inner membrane, nor other proteins. Bid, or its BH3-domain peptide, activated monomeric Bax to produce membrane openings that allowed the passage of very large (2 megadalton) dextran molecules, explaining the translocation of large mitochondrial proteins during apoptosis. This process required cardiolipin and was inhibited by antiapoptotic Bcl-xL. We conclude that mitochondrial protein release in apoptosis can be mediated by supramolecular openings in the outer mitochondrial membrane, promoted by BH3/Bax/lipid interaction and directly inhibited by Bcl-xL.
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