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Cytochrome c release precedes mitochondrial membrane potential loss in cerebellar granule neuron apoptosis: lack of mitochondrial swelling
Author(s) -
Wigdal Susan S.,
Kirkland Rebecca A.,
Franklin James L.,
HaakFrendscho Mary
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.01049.x
Subject(s) - mitochondrial permeability transition pore , mitochondrial apoptosis induced channel , mitochondrion , cytochrome c , microbiology and biotechnology , programmed cell death , apoptosis , biology , cycloheximide , inner mitochondrial membrane , membrane potential , biophysics , biochemistry , chemistry , protein biosynthesis
It has been suggested that release of cytochrome c (Cyt c ) from mitochondria during apoptotic death is through opening of the mitochondrial permeability transition pore followed by swelling‐induced rupture of the mitochondrial outer membrane. However, this remains controversial and may vary with cell type and model system. We determined that in mouse cerebellar granule neurons, Cyt c redistribution preceded the loss of mitochondrial membrane potential during the apoptotic process, suggesting that the pore did not open prior to release. Furthermore, when mitochondria were morphologically assessed by electron microscopy, they were not obviously swollen during the period of Cyt c release. This indicates that the pore mechanism of action, if any, is not through mitochondrial outer membrane rupture. While bongkrekic acid, an inhibitor of pore opening, modestly delayed apoptotic death, it also caused a significant ( p < 0.05) suppression of protein synthesis. An equivalent suppression of protein synthesis by cycloheximide had a similar delaying effect, suggesting that bongkrekic acid was acting non‐specifically. These findings suggest that mitochondrial permeability transition pore is not involved in Cyt c release from mitochondria during the apoptotic death of cerebellar granule neurons.