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Disruption of the outer mitochondrial membrane as a result of large amplitude swelling: the impact of irreversible permeability transition
Author(s) -
Petit Patrice X,
Goubern Marc,
Diolez Philippe,
Susin Santos A,
Zamzami Naoufal,
Kroemer Guido
Publication year - 1998
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(98)00318-4
Subject(s) - mitochondrial permeability transition pore , mitochondrion , cytochrome c , biophysics , chemistry , microbiology and biotechnology , bacterial outer membrane , programmed cell death , permeability (electromagnetism) , cytochrome , inner mitochondrial membrane , hepatocyte , membrane permeability , membrane potential , cytosol , apoptosome , apoptosis , biochemistry , membrane , biology , enzyme , caspase , in vitro , escherichia coli , gene
Upon induction of permeability transition with different agents (Ca 2+ , tert ‐butyl hydroperoxide, atractyloside), mouse hepatocyte mitochondria manifest a disruption of outer membrane integrity leading to the release of cytochrome c and apoptosis‐inducing factor (AIF), two proteins which are involved in programmed cell death (apoptosis). Chelation of Ca 2+ shortly (within 2 min) after its addition to isolated mitochondria reestablished the mitochondrial transmembrane potential (ΔΨ m ), prevented induction of large amplitude swelling and release of both cytochrome c and AIF. In contrast, late Ca 2+ chelation (10 min after addition of Ca 2+ ) failed to affect these parameters. Cytochrome c appears to be released through a mechanically damaged outer mitochondrial membrane rather than via a specific release mechanism. These findings clarify the mechanisms through which irreversible permeability transition occurs with subsequent large amplitude swelling culminating in the release of intermembrane proteins from mitochondria. Moreover, they confirm the hypothesis formulated by Skulachev [FEBS Lett. 397 (1996) 7–10 and Q. Rev. Biophys. 29 (1996) 169–202] linking permeability transition to activation of the apoptogenic catabolic enzymes.