THE COPPER CHAPERONE FOR SUPEROXIDE-DISMUTASE

Copper is distributed to distinct localizations in the cell through di verse pathways. We demonstrate here that the delivery of copper to cop per/zinc superoxide dismutase (SOD1) is mediated through a soluble fac tor identified as Saccharomyces cerevisiae LYS7 and human CCS (copper chaperone for SOD). This factor is specific for SOD1 and does not deli ver copper to proteins in the mitochondria, nucleus, or secretory path way. Yeast cells containing a lys7 Delta null mutation have normal lev els of SOD1 protein, but fail to incorporate copper into SOD1, which i s therefore devoid of superoxide scavenging activity. LYS7 and CCS spe cifically restore the biosynthesis of holoSOD1 in vivo. Elucidation of the CCS copper delivery pathway may permit development of novel thera peutic approaches to human diseases that involve SOD1, including amyot rophic lateral sclerosis.