Journal
CURRENT OPINION IN GENETICS & DEVELOPMENT
Volume 38, Issue -, Pages 45-51Publisher
CURRENT BIOLOGY LTD
DOI: 10.1016/j.gde.2016.03.006
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Funding
- National Institutes of Health [R37DK53953, R01GM107542]
- Friedreich's Ataxia Research Alliance
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Fe-S cluster assembly is an essential process for all cells. Impairment of Fe-S cluster assembly creates diseases in diverse and surprising ways. In one scenario, the loss of function of lipoic acid synthase, an enzyme with Fe-S cluster cofactor in mitochondria, impairs activity of various lipoamide-dependent enzymes with drastic consequences for metabolism. In a second scenario, the heme biosynthetic pathway in red cell precursors is specifically targeted, and iron homeostasis is perturbed, but lipoic acid synthesis is unaffected. In a third scenario, tRNA modifications arising from action of the cysteine desulfurase and/or Fe-S cluster proteins are lost, which may lead to impaired protein synthesis. These defects can then result in cancer, neurologic dysfunction or type 2 diabetes.
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