Human ISD11 is essential for both iron-sulfur cluster assembly and maintenance of normal cellular iron homeostasis
Copyright policy )Human ISD11 is essential for both iron-sulfur cluster assembly and maintenance of normal cellular iron homeostasis
The LYR family consists of proteins of diverse functions that contain the conserved tripeptide 'LYR' near the N-terminus, and it includes Isd11, which was previously observed to have an important role in iron-sulfur (Fe-S) cluster biogenesis in Saccharomyces cerevisiae. Here, we have cloned and characterized human ISD11 and shown that human ISD11 forms a stable complex in vivo with the human cysteine desulfurase (ISCS), which generates the inorganic sulfur needed for Fe-S protein biogenesis. Similar to ISCS, we have found that ISD11 localizes to the mitochondrial compartment, as expected, but also to the nucleus of mammalian cells. Using RNA-interference techniques, we have shown that suppression of human ISD11 inactivated mitochondrial and cytosolic aconitases. In addition, ISD11 suppression activated iron-responsive element-binding activity of iron regulatory protein 1, increased protein levels of iron regulatory protein 2, and resulted in abnormal punctate ferric iron accumulations in cells. These results indicate that ISD11 is important in the biogenesis of Fe-S clusters in mammalian cells, and its loss disrupts normal mitochondrial and cytosolic iron homeostasis.
- National Institute of Health Pakistan
Iron, Molecular Sequence Data, Iron-Regulatory Proteins, Mitochondria, Carbon-Sulfur Lyases, Protein Transport, Cytosol, Homeostasis, Humans, Amino Acid Sequence, Iron Regulatory Protein 1, Iron Regulatory Protein 2, Sequence Alignment, Sulfur, HeLa Cells
Iron, Molecular Sequence Data, Iron-Regulatory Proteins, Mitochondria, Carbon-Sulfur Lyases, Protein Transport, Cytosol, Homeostasis, Humans, Amino Acid Sequence, Iron Regulatory Protein 1, Iron Regulatory Protein 2, Sequence Alignment, Sulfur, HeLa Cells
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).133 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!