The Role of COA6 in the Mitochondrial Copper Delivery Pathway to Cytochrome <i>c</i> Oxidase
Copper is essential for the stability and activity of cytochrome <i>c</i> oxidase (CcO), the terminal enzyme of the mitochondrial respiratory chain. Copper is bound to COX1 and COX2, two core subunits of CcO, forming the Cu<sub>B</sub> and Cu<sub>A</sub> sites, re...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-01-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/1/125 |
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| author | Abhinav B. Swaminathan Vishal M. Gohil |
| author_facet | Abhinav B. Swaminathan Vishal M. Gohil |
| author_sort | Abhinav B. Swaminathan |
| collection | DOAJ |
| description | Copper is essential for the stability and activity of cytochrome <i>c</i> oxidase (CcO), the terminal enzyme of the mitochondrial respiratory chain. Copper is bound to COX1 and COX2, two core subunits of CcO, forming the Cu<sub>B</sub> and Cu<sub>A</sub> sites, respectively. Biogenesis of these two copper sites of CcO occurs separately and requires a number of evolutionarily conserved proteins that form the mitochondrial copper delivery pathway. Pathogenic mutations in some of the proteins of the copper delivery pathway, such as SCO1, SCO2, and COA6, have been shown to cause fatal infantile human disorders, highlighting the biomedical significance of understanding copper delivery mechanisms to CcO. While two decades of studies have provided a clearer picture regarding the biochemical roles of SCO1 and SCO2 proteins, some discrepancy exists regarding the function of COA6, the new member of this pathway. Initial genetic and biochemical studies have linked COA6 with copper delivery to COX2 and follow-up structural and functional studies have shown that it is specifically required for the biogenesis of the Cu<sub>A</sub> site by acting as a disulfide reductase of SCO and COX2 proteins. Its role as a copper metallochaperone has also been proposed. Here, we critically review the recent literature regarding the molecular function of COA6 in Cu<sub>A</sub> biogenesis. |
| first_indexed | 2024-03-10T01:50:36Z |
| format | Article |
| id | doaj.art-fbcd4576ab8e44d89a429c65afc15f3f |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T01:50:36Z |
| publishDate | 2022-01-01 |
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| spelling | doaj.art-fbcd4576ab8e44d89a429c65afc15f3f2023-11-23T13:07:27ZengMDPI AGBiomolecules2218-273X2022-01-0112112510.3390/biom12010125The Role of COA6 in the Mitochondrial Copper Delivery Pathway to Cytochrome <i>c</i> OxidaseAbhinav B. Swaminathan0Vishal M. Gohil1Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USADepartment of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USACopper is essential for the stability and activity of cytochrome <i>c</i> oxidase (CcO), the terminal enzyme of the mitochondrial respiratory chain. Copper is bound to COX1 and COX2, two core subunits of CcO, forming the Cu<sub>B</sub> and Cu<sub>A</sub> sites, respectively. Biogenesis of these two copper sites of CcO occurs separately and requires a number of evolutionarily conserved proteins that form the mitochondrial copper delivery pathway. Pathogenic mutations in some of the proteins of the copper delivery pathway, such as SCO1, SCO2, and COA6, have been shown to cause fatal infantile human disorders, highlighting the biomedical significance of understanding copper delivery mechanisms to CcO. While two decades of studies have provided a clearer picture regarding the biochemical roles of SCO1 and SCO2 proteins, some discrepancy exists regarding the function of COA6, the new member of this pathway. Initial genetic and biochemical studies have linked COA6 with copper delivery to COX2 and follow-up structural and functional studies have shown that it is specifically required for the biogenesis of the Cu<sub>A</sub> site by acting as a disulfide reductase of SCO and COX2 proteins. Its role as a copper metallochaperone has also been proposed. Here, we critically review the recent literature regarding the molecular function of COA6 in Cu<sub>A</sub> biogenesis.https://www.mdpi.com/2218-273X/12/1/125mitochondriacoppercytochrome <i>c</i> oxidaseCOA6COX2Cu<sub>A</sub> site |
| spellingShingle | Abhinav B. Swaminathan Vishal M. Gohil The Role of COA6 in the Mitochondrial Copper Delivery Pathway to Cytochrome <i>c</i> Oxidase Biomolecules mitochondria copper cytochrome <i>c</i> oxidase COA6 COX2 Cu<sub>A</sub> site |
| title | The Role of COA6 in the Mitochondrial Copper Delivery Pathway to Cytochrome <i>c</i> Oxidase |
| title_full | The Role of COA6 in the Mitochondrial Copper Delivery Pathway to Cytochrome <i>c</i> Oxidase |
| title_fullStr | The Role of COA6 in the Mitochondrial Copper Delivery Pathway to Cytochrome <i>c</i> Oxidase |
| title_full_unstemmed | The Role of COA6 in the Mitochondrial Copper Delivery Pathway to Cytochrome <i>c</i> Oxidase |
| title_short | The Role of COA6 in the Mitochondrial Copper Delivery Pathway to Cytochrome <i>c</i> Oxidase |
| title_sort | role of coa6 in the mitochondrial copper delivery pathway to cytochrome i c i oxidase |
| topic | mitochondria copper cytochrome <i>c</i> oxidase COA6 COX2 Cu<sub>A</sub> site |
| url | https://www.mdpi.com/2218-273X/12/1/125 |
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