Loss of cardiac mitochondrial complex I persulfidation impairs NAD+ homeostasis in aging
Protein persulfidation is a significant post-translational modification that involves addition of a sulfur atom to the cysteine thiol group and is facilitated by sulfide species. Persulfidation targets reactive cysteine residues within proteins, influencing their structure and/or function across var...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231723004159 |
| _version_ | 1797367733300494336 |
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| author | Maria-Kyriaki Drekolia Christina Karantanou Ilka Wittig Yuanyuan Li Dominik C. Fuhrmann Bernhard Brüne Antonia Katsouda Jiong Hu Andreas Papapetropoulos Sofia-Iris Bibli |
| author_facet | Maria-Kyriaki Drekolia Christina Karantanou Ilka Wittig Yuanyuan Li Dominik C. Fuhrmann Bernhard Brüne Antonia Katsouda Jiong Hu Andreas Papapetropoulos Sofia-Iris Bibli |
| author_sort | Maria-Kyriaki Drekolia |
| collection | DOAJ |
| description | Protein persulfidation is a significant post-translational modification that involves addition of a sulfur atom to the cysteine thiol group and is facilitated by sulfide species. Persulfidation targets reactive cysteine residues within proteins, influencing their structure and/or function across various biological systems. This modification is evolutionarily conserved and plays a crucial role in preventing irreversible cysteine overoxidation, a process that becomes prominent with aging. While, persulfidation decreases with age, its levels in the aged heart and the functional implications of such a reduction in cardiac metabolism remain unknown. Here we interrogated the cardiac persulfydome in wild-type adult mice and age-matched mice lacking the two sulfide generating enzymes, namely cystathionine gamma lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3MST). Our findings revealed that cardiac persulfidated proteins in wild type hearts are less abundant compared to those in other organs, with a primary involvement in mitochondrial metabolic processes. We further focused on one specific target, NDUFB7, which undergoes persulfidation by both CSE and 3MST derived sulfide species. In particular, persulfidation of cysteines C80 and C90 in NDUFB7 protects the protein from overoxidation and maintains the complex I activity in cardiomyocytes. As the heart ages, the levels of CSE and 3MST in cardiomyocytes decline, leading to reduced NDUFB7 persulfidation and increased cardiac NADH/NAD+ ratio. Collectively, our data provide compelling evidence for a direct link between cardiac persulfidation and mitochondrial complex I activity, which is compromised in aging. |
| first_indexed | 2024-03-08T17:22:25Z |
| format | Article |
| id | doaj.art-1cae94097bd34860a31485722c382ab7 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-03-08T17:22:25Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-1cae94097bd34860a31485722c382ab72024-01-03T04:12:33ZengElsevierRedox Biology2213-23172024-02-0169103014Loss of cardiac mitochondrial complex I persulfidation impairs NAD+ homeostasis in agingMaria-Kyriaki Drekolia0Christina Karantanou1Ilka Wittig2Yuanyuan Li3Dominik C. Fuhrmann4Bernhard Brüne5Antonia Katsouda6Jiong Hu7Andreas Papapetropoulos8Sofia-Iris Bibli9Department of Vascular Dysfunction, European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Frankfurt Am Main, GermanyDepartment of Vascular Dysfunction, European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Frankfurt Am Main, GermanyInstitute for Cardiovascular Physiology, Goethe-University Frankfurt, GermanyDepartment of Histology and Embryology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, Frankfurt, GermanyInstitute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, Frankfurt, GermanyClinical, Experimental Surgery and Translational Research Center, Biomedical Research Foundation of the Academy of Athens, Athens, Greece; Laboratory of Pharmacology, Department of Pharmacy, National and Kapodistrian University of Athens, Athens, GreeceInstitute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Frankfurt Am Main, Germany; Department of Histology and Embryology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaClinical, Experimental Surgery and Translational Research Center, Biomedical Research Foundation of the Academy of Athens, Athens, Greece; Laboratory of Pharmacology, Department of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece; Corresponding author. Laboratory of Pharmacology, Department of Pharmacy, National and Kapodistrian University of Athens, Athens, University Campus Zografou, 15771, Greece.Department of Vascular Dysfunction, European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Frankfurt Am Main, Germany; German Center of Cardiovascular Research (DZHK), Germany; Corresponding author. Department of Vascular Dysfunction, European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Ludolf-Krehl-Straße 13-17, 68167, Mannheim, Germany.Protein persulfidation is a significant post-translational modification that involves addition of a sulfur atom to the cysteine thiol group and is facilitated by sulfide species. Persulfidation targets reactive cysteine residues within proteins, influencing their structure and/or function across various biological systems. This modification is evolutionarily conserved and plays a crucial role in preventing irreversible cysteine overoxidation, a process that becomes prominent with aging. While, persulfidation decreases with age, its levels in the aged heart and the functional implications of such a reduction in cardiac metabolism remain unknown. Here we interrogated the cardiac persulfydome in wild-type adult mice and age-matched mice lacking the two sulfide generating enzymes, namely cystathionine gamma lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3MST). Our findings revealed that cardiac persulfidated proteins in wild type hearts are less abundant compared to those in other organs, with a primary involvement in mitochondrial metabolic processes. We further focused on one specific target, NDUFB7, which undergoes persulfidation by both CSE and 3MST derived sulfide species. In particular, persulfidation of cysteines C80 and C90 in NDUFB7 protects the protein from overoxidation and maintains the complex I activity in cardiomyocytes. As the heart ages, the levels of CSE and 3MST in cardiomyocytes decline, leading to reduced NDUFB7 persulfidation and increased cardiac NADH/NAD+ ratio. Collectively, our data provide compelling evidence for a direct link between cardiac persulfidation and mitochondrial complex I activity, which is compromised in aging.http://www.sciencedirect.com/science/article/pii/S2213231723004159PersulfidationCardiac agingCSE3MSTNDUFB7 |
| spellingShingle | Maria-Kyriaki Drekolia Christina Karantanou Ilka Wittig Yuanyuan Li Dominik C. Fuhrmann Bernhard Brüne Antonia Katsouda Jiong Hu Andreas Papapetropoulos Sofia-Iris Bibli Loss of cardiac mitochondrial complex I persulfidation impairs NAD+ homeostasis in aging Redox Biology Persulfidation Cardiac aging CSE 3MST NDUFB7 |
| title | Loss of cardiac mitochondrial complex I persulfidation impairs NAD+ homeostasis in aging |
| title_full | Loss of cardiac mitochondrial complex I persulfidation impairs NAD+ homeostasis in aging |
| title_fullStr | Loss of cardiac mitochondrial complex I persulfidation impairs NAD+ homeostasis in aging |
| title_full_unstemmed | Loss of cardiac mitochondrial complex I persulfidation impairs NAD+ homeostasis in aging |
| title_short | Loss of cardiac mitochondrial complex I persulfidation impairs NAD+ homeostasis in aging |
| title_sort | loss of cardiac mitochondrial complex i persulfidation impairs nad homeostasis in aging |
| topic | Persulfidation Cardiac aging CSE 3MST NDUFB7 |
| url | http://www.sciencedirect.com/science/article/pii/S2213231723004159 |
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