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Release of apoptogenic proteins from the mitochondrial intermembrane space during the mitochondrial permeability transition
Author(s) -
Scarlett Jared L,
Murphy Michael P
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)01391-4
Subject(s) - mitochondrial permeability transition pore , mitochondrial intermembrane space , intermembrane space , mitochondrial membrane transport protein , mitochondrial apoptosis induced channel , apoptosome , mitochondrion , microbiology and biotechnology , cytosol , cytochrome c , translocase of the inner membrane , cytoplasm , inner mitochondrial membrane , mitochondrial matrix , apoptosis , permeability (electromagnetism) , biology , mitochondrial carrier , biophysics , programmed cell death , biochemistry , bacterial outer membrane , membrane , caspase , escherichia coli , gene , enzyme
The Bcl‐2‐sensitive release of proteins such as cytochrome c from the mitochondrial intermembrane space into the cytosol is a critical early event in apoptosis. The mitochondrial permeability transition is also an important event in many forms of apoptotic cell death. To determine whether the permeability transition led to the release of apoptogenic proteins from mitochondria we induced the permeability transition in isolated rat liver mitochondria and characterised the proteins which were released. The permeability transition led to a generalised, non‐specific release of proteins, including cytochrome c , from the mitochondrial intermembrane space which was prevented by an inhibitor of the permeability transition. To determine the mechanism of this protein release we measured both mitochondrial matrix swelling and protein release during the permeability transition in media of different osmolarities. Protein release correlated with mitochondrial matrix swelling, therefore the permeability transition causes release of proteins from the intermembrane space by rupturing the mitochondrial outer membrane. Supporting an apoptotic role for the proteins released by this mechanism, supernatants from mitochondria undergoing the permeability transition caused apoptotic changes in isolated nuclei. These data support the proposal that the mitochondrial permeability transition can induce apoptosis by releasing apoptogenic proteins into the cytoplasm [Skulachev, V.P., FEBS Lett. 397 (1996) 7–10].