How proapoptotic proteins can escape from mitochondria? (Comment to Dr. D.W. Voehringer's paper, Free Radic. Biol. Med., 27, 945-950, 1999)

Some proapoptotic proteins (cytochrome c, apoptosis-inducing factor (AIF) a nd certain procaspases) are nornally localized in the intermembrane space o f mitochondria and escape to the cytosol when apoptosis is initiated. There are two mechanisms for release of the above proteins from mitochondria, na mely (i) an increase in permeability of the outer mitochondrial membrane fo r proteins, and (ii) an increase in permeability of the inner mitochondrial membrane for small solutes (permeability transition pore, PTP), causing sw elling of mitochondrial matrix, which in turn results in disruption of the outer membrane of the organelles. There is not a single piece of evidence f or localization of proapoptotic proteins in the matrix and their release vi a PTP to the cytosol as shown in a cartoon in Voehringer's paper. (C) 2000 Elsevier Science Inc.