LYR Motif Containing Protein 4 (LYRM4)

The deduced 91-amino acid human protein has a highly conserved LYR motif near its N terminus. Human ISD11 formed a stable complex in vivo with the human cysteine desulfurase (NFS1), which generates the inorganic sulfur needed for Fe/S protein biogenesis. Similar to NFS1, ISD11 localized to the mitochondrial compartment, but also to the nucleus of mammalian cells. Suppression of human ISD11 by siRNA inactivated mitochondrial and cytosolic aconitases. In addition, ISD11 suppression activated iron-responsive element-binding activity of iron regulatory protein-1 (ACO1), increased protein levels of iron regulatory protein-2 (IREB2), and resulted in abnormal punctate ferric iron accumulations in cells. ISD11 is important in the biogenesis of Fe/S clusters in mammalian cells, and its loss disrupts normal mitochondrial and cytosolic iron homeostasis.