References Friedrichs Ataxia

The import of metals into the mitochondria is poorly understood. Clearly with the generation of ROS it is essential that the presence of low-molecular-weight iron be kept to a minimum to prevent Fenton chemistry occurring. Iron is required by mitochondria for the biosynthesis of haem (Lange et al., 1999) and iron-sulfur proteins (Lill et al., 1999) (see Chapter 7). Experiments in yeast (Chapter 4) have shown that iron is not only imported into the mitochondrial matrix but is also transported out of the mitochondria across the inner membrane, constituting a veritable dynamic mitochondrial iron cycle (Radisky etal., 1999). The yeast gene YFH1 is homologous to the mammalian gene frataxin, which is mutated in Friedrich's ataxia. YFH1 is involved in mitochondrial iron efflux (Babcock et al., 1997); its deletion results in mitochondrial iron accumulation and ultimately respiratory incompetence. In man, frataxin, is localized to mitochondria, where it may play a role either in mitochondrial iron transport or in iron-sulfur cluster assembly or transport (Puccio and Koenig, 2000). Friedrich's ataxia (Chapter 7) is a mitochondrial disease associated with excessive mitochondrial accumulation of iron, particularly in brain and heart, leading to oxidative damage and mitochondrial dysfunction.

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