Coordination of metal center biogenesis in human cytochrome c oxidase.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35750769.
- Also identified by DOI 10.1038/s41467-022-31413-1 and PMC identifier 9232578.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Mitochondrial cytochrome c oxidase (CcO) or respiratory chain complex IV is a heme aa<sub>3</sub>-copper oxygen reductase containing metal centers essential for holo-complex biogenesis and enzymatic function that are assembled by subunit-specific metallochaperones. The enzyme has two copper sites located in the catalytic core subunits. The COX1 subunit harbors the Cu<sub>B</sub> site that tightly associates with heme a<sub>3</sub> while the COX2 subunit contains the binuclear Cu<sub>A</sub> site. Here, we report that in human cells the CcO copper chaperones form macromolecular assemblies and cooperate with several twin CX<sub>9</sub>C proteins to control heme a biosynthesis and coordinate copper transfer sequentially to the Cu<sub>A</sub> and Cu<sub>B</sub> sites. These data on CcO illustrate a mechanism that regulates the biogenesis of macromolecular enzymatic assemblies with several catalytic metal redox centers and prevents the accumulation of cytotoxic reactive assembly intermediates.
Medical subject headings
- Electron Transport Complex IV
- Oxidoreductases