R Abeti, M H Parkinson, I P Hargreaves, P R Angelova, C Sandi, M A Pook, P Giunti and A Y Abramov. Cell Death and Disease (2016) 7, e2237; doi:10.1038/cddis.2016.111 Published online 26 May 2016
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Although the role of frataxin is largely known, being fundamental for the iron biogenesis in the cell, the relation between frataxin and mitochondrial bioenergetics is not completely clear.
We assessed the type of mitochondrial dysfunction that was present in the cerebellum, concluding that Complex I activity is impaired, but Complex II compensates by overworking. Therefore, if we consider the ETC, we can define the mitochondrial dysfunction as a mildly defective bioenergetic phenotype. However, this mild dysfunction drives the formation of free radicals that cannot be attenuated by the endogenous antioxidant systems, which are downregulated. Thus, the level of lipid peroxidation increases dramatically, damaging the cells and causing premature cell death. Therefore, lipid peroxidation could be a potential target for future therapeutic approaches in FRDA.
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