Reversible changes in the redox state of cysteine residues represent an important mechanism with which to regulate protein function. In mitochondria, such redox reactions modulate the localization or activity of a group of proteins, most of which function in poorly defined pathways with essential roles in copper delivery to cytochrome c oxidase (COX) during holoenzyme biogenesis. To date, a total of 8 soluble (COX17, COX19, COX23, PET191, CMC1-4) and 3 integral membrane (COX11, SCO1, SCO2) accessory proteins with cysteine-containing domains that reside within the mitochondrial intermembrane space (IMS) have been identified in yeast, all of which have human orthologues. Compelling evidence from studies of COX17, SCO1, and SCO2 argues that regulation of the redox state of their cysteines is integral to their metallochaperone function. Redox also appears to be crucial to the regulation of a SCO-dependent, mitochondrial signaling pathway that modulates the rate of copper efflux from the cell. Here, I review our understanding of redox-dependent modulation of copper delivery to COX and IMS-localized copper-zinc superoxide dismutase (SOD1) during the maturation of each enzyme, and discuss how this in turn may serve to functionally couple mitochondrial copper handling pathways with those localized elsewhere in the cell to regulate cellular copper homeostasis.
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| Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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| Site | Modification | Modifier | Source | Reference |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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| Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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| Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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