title: Metabolic regulation of citrate and iron by aconitases: role of iron-sulfur cluster biogenesis.
abstract: Iron and citrate are essential for the metabolism of most organisms, and regulation of iron and citrate biology at both the cellular and systemic levels is critical for normal physiology and survival. Mitochondrial and cytosolic aconitases catalyze the interconversion of citrate and isocitrate, and aconitase activities are affected by iron levels, oxidative stress and by the status of the Fe-S cluster biogenesis apparatus. Assembly and disassembly of Fe-S clusters is a key process not only in regulating the enzymatic activity of mitochondrial aconitase in the citric acid cycle, but also in controlling the iron sensing and RNA binding activities of cytosolic aconitase (also known as iron regulatory protein IRP1). This review discusses the central role of aconitases in intermediary metabolism and explores how iron homeostasis and Fe-S cluster biogenesis regulate the Fe-S cluster switch and modulate intracellular citrate flux.
authors.affiliation: Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, NIH Bldg 18, Rm 101, Bethesda, MD 20892, USA.
authors.forename: Wing-Hang
authors.initials: WH
authors.lastname: Tong
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Rouault
mesh_terms: D000154:Aconitate Hydratase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002614:Chelating Agents / Q000378:metabolism; D019343:Citric Acid / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004734:Energy Metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress
chemical_list: D002614:Chelating Agents; D007506:Iron-Sulfur Proteins; D019343:Citric Acid; D007501:Iron; D000154:Aconitate Hydratase