A Role for IOP1 in Mammalian Cytosolic Iron-Sulfur Protein Biogenesis

• Published in: The Journal of biological chemistry Vol. 283; no. 14; pp. 9231 - 9238
• Main Authors: Song, Daisheng, Lee, Frank S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.04.2008; American Society for Biochemistry and Molecular Biology
• Subjects: Aconitate Hydratase - biosynthesis; Aconitate Hydratase - genetics; Apoferritins - biosynthesis; Apoferritins - genetics; Bacteria, Anaerobic - genetics; Bacteria, Anaerobic - metabolism; Cytosol - metabolism; HeLa Cells; Humans; Hydrogenase - genetics; Hydrogenase - metabolism; Iron - metabolism; Iron Regulatory Protein 1 - biosynthesis; Iron Regulatory Protein 1 - genetics; Iron-Sulfur Proteins - genetics; Iron-Sulfur Proteins - metabolism; Metalloproteins - biosynthesis; Metalloproteins - genetics; Mitochondria - genetics; Mitochondria - metabolism; Protein Biosynthesis - physiology; Receptors, Transferrin - biosynthesis; Receptors, Transferrin - genetics; RNA Interference; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Sequence Homology, Amino Acid; Sulfur - metabolism; Xanthine Oxidase - biosynthesis; Xanthine Oxidase - genetics
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M708077200

The biogenesis of cytosolic iron-sulfur (Fe-S) proteins in mammalian cells is poorly understood. In Saccharomyces cerevisiae, there is a pathway dedicated to cytosolic Fe-S protein maturation that involves several essential proteins. One of these is Nar1, which intriguingly is homologous to iron-only hydrogenases, ancient enzymes that catalyze the formation of hydrogen gas in anaerobic bacteria. There are two orthologues of Nar1 in mammalian cells, iron-only hydrogenase-like protein 1 (IOP1) and IOP2 (also known as nuclear prelamin A recognition factor). We examined IOP1 for a potential role in mammalian cytosolic Fe-S protein biogenesis. We found that knockdown of IOP1 in both HeLa and Hep3B cells decreases the activity of cytosolic aconitase, an Fe-S protein, but not that of mitochondrial aconitase. Knockdown of IOP2, in contrast, had no effect on either. The decrease in aconitase activity upon IOP1 knockdown is rescued by expression of a small interference RNA-resistant version of IOP1. Upon loss of its Fe-S cluster, cytosolic aconitase is known to be converted to iron regulatory protein 1, and consistent with this, we found that IOP1 knockdown increases transferrin receptor 1 mRNA levels and decreases ferritin heavy chain protein levels. IOP1 knockdown also leads to a decrease in activity of xanthine oxidase, a distinct cytosolic Fe-S protein. Taken together, these results provide evidence that IOP1 is involved in mammalian cytosolic Fe-S protein maturation.