Absence of mitochondrial CX9C-CX10C protein Cox12 generates oxidative and nitrosative stress in Saccharomyces cerevisiae: Implication on cellular redox homeostasis
Mitochondrial intermembrane space (IMS) harbors a series of small, evolutionarily conserved redox-active cysteine-rich proteins. These proteins are essential for the functioning of cytochrome c oxidase, but their role in maintaining cellular redox processes is unknown. Here, we find out that in the...
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Elsevier
2024-12-01
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| Series: | Advances in Redox Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667137924000195 |
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| author | Soumyajit Mukherjee Shubhojit Das Sourav Kumar Patra Mayukh Das Sanjay Ghosh Alok Ghosh |
| author_facet | Soumyajit Mukherjee Shubhojit Das Sourav Kumar Patra Mayukh Das Sanjay Ghosh Alok Ghosh |
| author_sort | Soumyajit Mukherjee |
| collection | DOAJ |
| description | Mitochondrial intermembrane space (IMS) harbors a series of small, evolutionarily conserved redox-active cysteine-rich proteins. These proteins are essential for the functioning of cytochrome c oxidase, but their role in maintaining cellular redox processes is unknown. Here, we find out that in the absence of two such cysteine-rich Cx9C-Cx10C proteins, cytochrome c oxidase subunit 12 (Cox12) or cytochrome c oxidase assembly factor 6 (Coa6), Saccharomyces cerevisiae cells become sensitive under the oxidative and nitrosative stress. Interestingly, knockout of COX12 generates a significant amount of endogenous reactive oxygen species (ROS) and reactive nitrogen species (RNS) as evidenced by FACS analysis. Moreover, cellular redox status, redox-active enzymes glutathione reductase, catalase, S-nitroso glutathione reductase, and protein nitration were significantly affected in Cox12 null cells. Further, we found that an overexpression of COX12 partially protects mitochondrial respiratory subunit Sdh2 under oxidative and nitrosative stress. Taken together, we provide proof of evidence that cysteine-rich proteins in the IMS dynamically control the cellular redox milieu and actively prevent reactive nitrogen and oxygen species generation. |
| format | Article |
| id | doaj-art-798064ff94d142ccb2dc4583c4c0b958 |
| institution | Kabale University |
| issn | 2667-1379 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Advances in Redox Research |
| spelling | doaj-art-798064ff94d142ccb2dc4583c4c0b9582024-12-12T05:24:00ZengElsevierAdvances in Redox Research2667-13792024-12-0113100112Absence of mitochondrial CX9C-CX10C protein Cox12 generates oxidative and nitrosative stress in Saccharomyces cerevisiae: Implication on cellular redox homeostasisSoumyajit Mukherjee0Shubhojit Das1Sourav Kumar Patra2Mayukh Das3Sanjay Ghosh4Alok Ghosh5Department of Biochemistry, University of Calcutta, 35 Ballygunge Circular Road, Kolkata 700019, IndiaDepartment of Biochemistry, University of Calcutta, 35 Ballygunge Circular Road, Kolkata 700019, India; Department of Biochemistry, Ramkrishna Ashram Diagnostic and Research Institute, Nimpith 743338, IndiaDepartment of Biochemistry, University of Calcutta, 35 Ballygunge Circular Road, Kolkata 700019, India; Post Doctoral Research Associate, Dept. of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, USADepartment of Biochemistry, University of Calcutta, 35 Ballygunge Circular Road, Kolkata 700019, IndiaDepartment of Biochemistry, University of Calcutta, 35 Ballygunge Circular Road, Kolkata 700019, IndiaDepartment of Biochemistry, University of Calcutta, 35 Ballygunge Circular Road, Kolkata 700019, India; Corresponding author at: Department of Biochemistry, University of Calcutta, 35 Ballygunge Circular Road, Kolkata 700019, India.Mitochondrial intermembrane space (IMS) harbors a series of small, evolutionarily conserved redox-active cysteine-rich proteins. These proteins are essential for the functioning of cytochrome c oxidase, but their role in maintaining cellular redox processes is unknown. Here, we find out that in the absence of two such cysteine-rich Cx9C-Cx10C proteins, cytochrome c oxidase subunit 12 (Cox12) or cytochrome c oxidase assembly factor 6 (Coa6), Saccharomyces cerevisiae cells become sensitive under the oxidative and nitrosative stress. Interestingly, knockout of COX12 generates a significant amount of endogenous reactive oxygen species (ROS) and reactive nitrogen species (RNS) as evidenced by FACS analysis. Moreover, cellular redox status, redox-active enzymes glutathione reductase, catalase, S-nitroso glutathione reductase, and protein nitration were significantly affected in Cox12 null cells. Further, we found that an overexpression of COX12 partially protects mitochondrial respiratory subunit Sdh2 under oxidative and nitrosative stress. Taken together, we provide proof of evidence that cysteine-rich proteins in the IMS dynamically control the cellular redox milieu and actively prevent reactive nitrogen and oxygen species generation.http://www.sciencedirect.com/science/article/pii/S2667137924000195Cytochrome c oxidase subunit 12 (Cox12)Mitochondrial respirationCellular redox statusOxidative and nitrosative stresses |
| spellingShingle | Soumyajit Mukherjee Shubhojit Das Sourav Kumar Patra Mayukh Das Sanjay Ghosh Alok Ghosh Absence of mitochondrial CX9C-CX10C protein Cox12 generates oxidative and nitrosative stress in Saccharomyces cerevisiae: Implication on cellular redox homeostasis Advances in Redox Research Cytochrome c oxidase subunit 12 (Cox12) Mitochondrial respiration Cellular redox status Oxidative and nitrosative stresses |
| title | Absence of mitochondrial CX9C-CX10C protein Cox12 generates oxidative and nitrosative stress in Saccharomyces cerevisiae: Implication on cellular redox homeostasis |
| title_full | Absence of mitochondrial CX9C-CX10C protein Cox12 generates oxidative and nitrosative stress in Saccharomyces cerevisiae: Implication on cellular redox homeostasis |
| title_fullStr | Absence of mitochondrial CX9C-CX10C protein Cox12 generates oxidative and nitrosative stress in Saccharomyces cerevisiae: Implication on cellular redox homeostasis |
| title_full_unstemmed | Absence of mitochondrial CX9C-CX10C protein Cox12 generates oxidative and nitrosative stress in Saccharomyces cerevisiae: Implication on cellular redox homeostasis |
| title_short | Absence of mitochondrial CX9C-CX10C protein Cox12 generates oxidative and nitrosative stress in Saccharomyces cerevisiae: Implication on cellular redox homeostasis |
| title_sort | absence of mitochondrial cx9c cx10c protein cox12 generates oxidative and nitrosative stress in saccharomyces cerevisiae implication on cellular redox homeostasis |
| topic | Cytochrome c oxidase subunit 12 (Cox12) Mitochondrial respiration Cellular redox status Oxidative and nitrosative stresses |
| url | http://www.sciencedirect.com/science/article/pii/S2667137924000195 |
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