ArticleHuman molecular genetics2016
Mitochondrial disease genes COA6, COX6B and SCO2 have overlapping roles in COX2 biogenesis.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 55 citations in OpenAlex.
- Association of Copper with Atherosclerosis and Treatment Strategies.Journal of cardiovascular translational research · 2025Review
- A high copy suppressor screen identifies factors enhancing the allotopic production of subunit II of cytochrome c oxidase.G3 (Bethesda, Md.) · 2025Article
- Oxidative phosphorylation related gene COA6 is a novel indicator for the prognosis and immune response in lung adenocarcinoma.Scientific reports · 2024Article
- Identification of factors limiting the allotopic production of the Cox2 subunit of yeast cytochrome c oxidase.Genetics · 2024Article
- More than Just Bread and Wine: Using Yeast to Understand Inherited Cytochrome Oxidase Deficiencies in Humans.International journal of molecular sciences · 2024Review
- Review
- The [PSIMolecular biology of the cell · 2022Article
- A yeast suppressor screen links Coa4 to the mitochondrial copper delivery pathway for cytochrome c oxidase.Genetics · 2022Article
- Structures ofScience (New York, N.Y.) · 2022Article
- The Role of COA6 in the Mitochondrial Copper Delivery Pathway to CytochromeBiomolecules · 2022Review
- Prime Real Estate: Metals, Cofactors and MICOS.Frontiers in cell and developmental biology · 2022Review
- The Power of Yeast in Modelling Human Nuclear Mutations Associated with Mitochondrial Diseases.Genes · 2021Review
- Review
- Getting out what you put in: Copper in mitochondria and its impacts on human disease.Biochimica et biophysica acta. Molecular cell research · 2021Review
- Redox-Mediated Regulation of Mitochondrial Biogenesis, Dynamics, and Respiratory Chain Assembly in Yeast and Human Cells.Frontiers in cell and developmental biology · 2021Review
- HIGD-Driven Regulation of CytochromeCells · 2020Review
- What Role Does COA6 Play in CytochromeInternational journal of molecular sciences · 2020Review
- Mitochondrial OXPHOS Biogenesis: Co-Regulation of Protein Synthesis, Import, and Assembly Pathways.International journal of molecular sciences · 2020Review
- COA6 Facilitates Cytochrome c Oxidase Biogenesis as Thiol-reductase for Copper Metallochaperones in Mitochondria.Journal of molecular biology · 2020Article
- Structural and functional characterization of the mitochondrial complex IV assembly factor Coa6.Life science alliance · 2019Article
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Authors and funding
7 authors at 1 institution in 1 country.
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Abstract
Biogenesis of cytochrome c oxidase (CcO), the terminal enzyme of the mitochondrial respiratory chain, is a complex process facilitated by several assembly factors. Pathogenic mutations were recently reported in one such assembly factor, COA6, and our previous work linked Coa6 function to mitochondrial copper metabolism and expression of Cox2, a copper-containing subunit of CcO. However, the precise role of Coa6 in Cox2 biogenesis remained unknown. Here we show that yeast Coa6 is an orthologue of human COA6, and like Cox2, is regulated by copper availability, further implicating it in copper delivery to Cox2. In order to place Coa6 in the Cox2 copper delivery pathway, we performed a comprehensive genetic epistasis analysis in the yeast Saccharomyces cerevisiae and found that simultaneous deletion of Coa6 and Sco2, a mitochondrial copper metallochaperone, or Coa6 and Cox12/COX6B, a structural subunit of CcO, completely abrogates Cox2 biogenesis. Unlike Coa6 deficient cells, copper supplementation fails to rescue Cox2 levels of these double mutants. Overexpression of Cox12 or Sco proteins partially rescues the coa6Δ phenotype, suggesting their overlapping but non-redundant roles in copper delivery to Cox2. These genetic data are strongly corroborated by biochemical studies demonstrating physical interactions between Coa6, Cox2, Cox12 and Sco proteins. Furthermore, we show that patient mutations in Coa6 disrupt Coa6-Cox2 interaction, providing the biochemical basis for disease pathogenesis. Taken together, these results place COA6 in the copper delivery pathway to CcO and, surprisingly, link it to a previously unidentified function of CcO subunit Cox12 in Cox2 biogenesis.
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