Cytochrome c release precedes mitochondrial membrane potential loss in cerebellar granule neuron apoptosis: lack of mitochondrial swelling
Article first published online: 3 FEB 2004
Journal of Neurochemistry
Volume 82, Issue 5, pages 1029–1038, September 2002
How to Cite
Wigdal, S. S., Kirkland, R. A., Franklin, J. L. and Haak-Frendscho, M. (2002), Cytochrome c release precedes mitochondrial membrane potential loss in cerebellar granule neuron apoptosis: lack of mitochondrial swelling. Journal of Neurochemistry, 82: 1029–1038. doi: 10.1046/j.1471-4159.2002.01049.x
- Issue published online: 3 FEB 2004
- Article first published online: 3 FEB 2004
- Received January 3, 2002; revised manuscript received May 10, 2002; accepted May 10, 2002.
- cerebellar granule neuron (CGN);
- cytochrome c;
- electron microscopy;
- mitochondrial permeability transition pore (MPTP)
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.