Iron mediated toxicity and programmed cell death: A review and a re-examination of existing paradigms

Rawan Eid, Nagla T.T. Arab, Michael T. Greenwood, Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1864, Issue 2, February 2017, Pages 399-430, ISSN 0167-4889, doi:10.1016/j.bbamcr.2016.12.002.

Friedreich's ataxia is another example of a recessive mutation, the mutation results in a dramatic reduction in the expression of frataxin. Frataxin is thought to store iron and to promote Fe-S cluster assembly. In yeast, the overexpression the iron binding prosurvival ferritin serve to increase the viability of cells lacking frataxin while iron chelators are shown to protect cultured cell and animal models of Friedreich's ataxia. In spite of what appears to be iron overload mediated cell death iron chelator have very little therapeutic value. More likely the lack of frataxin is leading to stress, and increase in redox active iron and the induction of PCD. Thus the overexpression of genes encoding proteins with pro-survival or anti-oxidant functions, including ferritin, as well as anti-oxidants may protect from the decrease in frataxin levels.