Both human ferredoxins 1 and 2 and ferredoxin reductase are important for iron-sulfur cluster biogenesis

	Both human ferredoxins 1 and 2 and ferredoxin reductase are important for iron-sulfur cluster biogenesis
	Shi, YB; Ghosh, M; Kovtunovych, G; Crooks, DR; Rouault, TA
刊名	BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
	2012
卷号	1823 期号:2 页码:484-492
关键词	Iron-sulfur cluster biogenesis RNAi Mitochondrial iron accumulation Heme biosynthesis Cellular iron homeostasis
通讯作者	Rouault, TA (reprint author), NICHHD, Program Mol Med, Bethesda, MD 20892 USA.,trou@helix.nih.gov
英文摘要	Ferredoxins are iron-sulfur proteins that have been studied for decades because of their role in facilitating the monooxygenase reactions catalyzed by p450 enzymes. More recently, studies in bacteria and yeast have demonstrated important roles for ferredoxin and ferredoxin reductase in iron-sulfur cluster assembly. The human genome contains two homologous ferredoxins, ferredoxin 1 (FDX1) and ferredoxin 2 (FDX2 - formerly known as ferredoxin 1L). More recently, the roles of these two human ferredoxins in iron-sulfur cluster assembly were assessed, and it was concluded that FDX1 was important solely for its interaction with p450 enzymes to synthesize mitochondrial steroid precursors, whereas FDX2 was used for synthesis of iron-sulfur clusters, but not steroidogenesis. To further assess the role of the FDX-FDXR system in mammalian iron-sulfur cluster biogenesis, we performed siRNA studies on FDX1 and FDX2, on several human cell lines, using oligonucleotides identical to those previously used, along with new oligonucleotides that specifically targeted each gene. We concluded that both FDX1 and FDX2 were important in iron-sulfur cluster biogenesis. Loss of FDX1 activity disrupted activity of iron-sulfur cluster enzymes and cellular iron homeostasis, causing mitochondrial iron overload and cytosolic iron depletion. Moreover, knockdown of the sole human ferredoxin reductase, FDXR, diminished iron-sulfur cluster assembly and caused mitochondrial iron overload in conjunction with cytosolic depletion. Our studies suggest that interference with any of the three related genes, FDX1, FDX2 or FDXR, disrupts iron-sulfur cluster assembly and maintenance of normal cytosolic and mitochondrial iron homeostasis. Published by Elsevier B.V.
学科主题	Biochemistry & Molecular Biology; Cell Biology
类目[WOS]	Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]	SACCHAROMYCES-CEREVISIAE ; AZOTOBACTER-VINELANDII ; ADRENODOXIN REDUCTASE ; ESSENTIAL GENE ; PROTEIN ; MITOCHONDRIAL ; HOMEOSTASIS ; HEME ; DISEASE ; CODES
收录类别	SCI
语种	英语
WOS记录号	WOS:000301155700031
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/546]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Shi, YB,Ghosh, M,Kovtunovych, G,et al. Both human ferredoxins 1 and 2 and ferredoxin reductase are important for iron-sulfur cluster biogenesis[J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH,2012,1823(2):484-492.
APA	Shi, YB,Ghosh, M,Kovtunovych, G,Crooks, DR,&Rouault, TA.(2012).Both human ferredoxins 1 and 2 and ferredoxin reductase are important for iron-sulfur cluster biogenesis.BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH,1823(2),484-492.
MLA	Shi, YB,et al."Both human ferredoxins 1 and 2 and ferredoxin reductase are important for iron-sulfur cluster biogenesis".BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH 1823.2(2012):484-492.