title: Roles of Fe-S proteins: from cofactor synthesis to iron homeostasis to protein synthesis.
abstract: 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.
authors.affiliation: Department of Pharmacology, Physiology, and Neuroscience, New Jersey Medical School, Rutgers University, Newark, NJ 07101, USA.
authors.forename: Debkumar
authors.initials: D
authors.lastname: Pain
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: adancis@mail.med.upenn.edu.
authors.forename: Andrew
authors.initials: A
authors.lastname: Dancis
mesh_terms: D013437:Carbon-Sulfur Lyases / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D006418:Heme / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007506:Iron-Sulfur Proteins / Q000235:genetics* / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D005810:Multigene Family; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis / Q000235:genetics; D012343:RNA, Transfer / Q000235:genetics; D013466:Sulfurtransferases / Q000235:genetics
chemical_list: D007506:Iron-Sulfur Proteins; D006418:Heme; D012343:RNA, Transfer; D007501:Iron; D013466:Sulfurtransferases; C116435:lipoic acid synthase; D013437:Carbon-Sulfur Lyases; C080546:cysteine desulfurase