Juan A. Navarro and Stephan Schneuwly; Front Genet. 2017; 8: 223. Published online 2017 December 21. doi: 10.3389/fgene.2017.00223
Similar contradictory findings have been recently described in a Drosophila model of Friedreich's ataxia (FRDA). Impairment of transcription of the gene frataxin is the molecular cause underlying the disease. Most of the current evidences support a strong relation between frataxin and iron in several models, including the fly. Moreover, genetic and chemical manipulation of iron biology was found to have a positive impact in FRDA phenotypes. Remarkably, flies displaying reduced levels of frataxin also seemed to have altered levels of other metals such as Zn and Cu. Although the contribution of other metals was already suggested by studies in human samples, this fly work was the first one showing that therapies based on such metals might be beneficial. Indeed, Zn and Cu chelators improved frataxin deficiency without altering iron content. In this line, silencing either dZip42C.1, dZip42C.2 and dZip88E or dZnT35C, dZnT41F and dZnT63C also improved FRDA conditions via reduction of the iron content. All these results raise several interesting questions: Why are Cu and Zn accumulating in FRDA flies? Why does KD of genes with opposite function or acting in different cellular compartments trigger the same effect? Did they also modify the accumulation of Zn in FRDA flies? Is it possible that any of these transporters has also a mitochondrial function?
Thursday, January 11, 2018
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