Coordination of Metal Center Biogenesis in Human Cytochrome C Oxidase

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Jun 24

PMID 35750769

Authors

Eva Nyvltova

Jonathan V Dietz

Javier Seravalli

Oleh Khalimonchuk

Antoni Barrientos

Affiliations

Soon will be listed here.

Abstract

Mitochondrial cytochrome c oxidase (CcO) or respiratory chain complex IV is a heme aa-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 site that tightly associates with heme a while the COX2 subunit contains the binuclear Cu site. Here, we report that in human cells the CcO copper chaperones form macromolecular assemblies and cooperate with several twin CXC proteins to control heme a biosynthesis and coordinate copper transfer sequentially to the Cu and Cu 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.

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