Summary
The pathogenesis of mitochondrial disorders has largely focused on the impairment of cellular energy metabolism. However, mitochondrial dysfunction has also been implicated as a factor in the initiation of apoptosis due to the translocation of cytochrome c, from mitochondria to the cytosol, and the subsequent cleavage of pro-caspase 3. In this study, we determined the cytochrome c content of cytosols (skeletal muscle) prepared from 22 patients with evidence of compromised mitochondrial electron transport chain enzyme activity and 26 disease controls. The cytochrome c content of the mitochondrial electron transport chain-deficient group was found to be significantly (p < 0.02) elevated when compared with the control group (63.7 ± 15.5 versus 27.7 ± 2.5 ng/mg protein). Furthermore, a relationship between the cytosolic cytochrome c content of skeletal muscle and complex I and complex IV activities was demonstrated. Such data raise the possibility that mitochondrial cytochrome c release may be a feature of mitochondrial disorders, particularly for those patients with marked deficiencies of respiratory chain enzymes. Whether initiation of apoptosis occurs as a direct consequence of this cytochrome c release has not been fully evaluated here. However, for one patient with the greatest documented cytosolic cytochrome c content, caspase 3 could be demonstrated in the cytosolic preparation. Further work is required in order to establish whether a relationship also exists between caspase 3 formation and the magnitude of respiratory chain deficiency.
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Abbreviations
- ETC:
-
electron transport chain
- mtDNA:
-
mitochondrial DNA
- SEM:
-
standard error of the mean
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Communicating editor: Wolfgang Sperl
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Oppenheim, M.L.S., Hargreaves, I.P., Pope, S. et al. Mitochondrial cytochrome c release: a factor to consider in mitochondrial disease?. J Inherit Metab Dis 32, 269–273 (2009). https://doi.org/10.1007/s10545-009-1061-8
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DOI: https://doi.org/10.1007/s10545-009-1061-8