Mitochondrial copper metabolism and delivery to cytochrome c oxidase

Abstract

SummaryMetals are essential elements of all living organisms. Among them, copper is required for a multiplicity of functions including mitochondrial oxidative phosphorylation and protection against oxidative stress. Here we will focus on describing the pathways involved in the delivery of copper to cytochrome c oxidase (COX), a mitochondrial metalloenzyme acting as the terminal enzyme of the mitochondrial respiratory chain. The catalytic core of COX is formed by three mitochondriallyencoded subunits and contains three copper atoms. Two copper atoms bound to subunit 2 constitute the Cu A site, the primary acceptor of electrons from ferrocytochrome c. The third copper, Cu B , is associated with the high-spin heme a 3 group of subunit 1. Recent studies, mostly performed in the yeast Saccharomyces cerevisiae, have provided new clues about 1) the source of the copper used for COX metallation; 2) the roles of Sco1p and Cox11p, the proteins involved in the direct delivery of copper to the Cu A and Cu B sites, respectively; 3) the action mechanism of Cox17p, a copper chaperone that provides copper to Sco1p and Cox11p; 4) the existence of at least four Cox17p homologues carrying a similar twin CX 9 C domain suggestive of metal binding, Cox19p, Cox23p, Pet191p and Cmc1p, that could be part of the same pathway; and 5) the presence of a disulfide relay system in the intermembrane space of mitochondria that mediates import of proteins with conserved cysteines motifs such as the CX 9 C characteristic of Cox17p and its homologues. The different pathways are reviewed and discussed in the context of both mitochondrial COX assembly and copper homeostasis.2008 IUBMB IUBMB Life, 60(7): [421][422][423][424][425][426][427][428][429] 2008

Hepatoprotective effects of cod liver oil against sodium nitrite toxicity in rats

“…Mitochondrial cytochrome c oxidase is the final electron acceptor in the mitochondrial electron transport chain and is required for aerobic ATP production through catalyzes of electron transfer from cytochrome c to molecular oxygen (Horn et al, 2008). We found a significant decrease in the cytochrome c oxidase activity in rats that received oral sodium nitrite.…”

The Conserved Mitochondrial Twin Cx9C Protein Cmc2 Is a Cmc1 Homologue Essential for Cytochrome c Oxidase Biogenesis

“…In ⌬cmc1 cells, Sod1 activity is increased, whereas in cells overexpressing Cmc1, Sod1 activity is decreased (19). These observations allowed us to propose that from its location on the IMS face of the inner mitochondrial membrane, Cmc1 could be involved in controlling copper traffic from the matrix to the respective COX and Sod1 metallochaperones located in the IMS (3,19). Now we have explored whether Cmc2 is involved in a similar role.…”

“…Both COX and mitochondrial Sod1 receive copper within the mitochondrial IMS through pathways involving the assistance of evolutionary conserved enzyme-specific copper chaperones localized to this compartment (3,4). Sod1 copper insertion requires the specific copper chaperone Ccs1 (5), a portion of which is localized to the mitochondrial IMS (2,6).…”

Structure and Mode of Action of Microplusin, a Copper II-chelating Antimicrobial Peptide from the Cattle Tick Rhipicephalus (Boophilus) microplus

“…Copper II is essential for proper assembly and functioning of terminal oxidases of the electron transport chain (53). Results in Table 3 It is noteworthy that cyanide-resistant respiration (residual respiration after KCN addition) in the three conditions tested was intact, indicating that only cyanide-sensitive respiration was affected by chronic exposure to microplusin.…”