Cardiomyocyte-specific deletion of GCN5L1 reduces lysine acetylation and attenuates diastolic dysfunction in aged mice by improving cardiac fatty acid oxidation
© 2024 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society..
Cardiac mitochondrial dysfunction is a critical contributor to the pathogenesis of aging and many age-related conditions. As such, complete control of mitochondrial function is critical to maintain cardiac efficiency in the aged heart. Lysine acetylation is a reversible post-translational modification shown to regulate several mitochondrial metabolic and biochemical processes. In the present study, we investigated how mitochondrial lysine acetylation regulates fatty acid oxidation (FAO) and cardiac function in the aged heart. We found a significant increase in mitochondrial protein acetylation in the aged heart which correlated with increased level of mitochondrial acetyltransferase-related protein GCN5L1. We showed that acetylation status of several fatty acid and glucose oxidation enzymes (long-chain acyl-coenzyme A dehydrogenase, hydroxyacyl-coA dehydrogenase, and pyruvate dehydrogenase) were significantly up-regulated in aged heart which correlated with decreased enzymatic activities. Using a cardiac-specific GCN5L1 knockout (KO) animal model, we showed that overall acetylation of mitochondrial proteins was decreased in aged KO animals, including FAO proteins which led to improved FAO activity and attenuated cardiac diastolic dysfunction observed in the aged heart. Together, these findings indicate that lysine acetylation regulates FAO in the aged heart which results in improved cardiac diastolic function and this is in part regulated by GCN5L1.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:481 |
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| Enthalten in: |
The Biochemical journal - 481(2024), 6 vom: 20. März, Seite 423-436 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Stewart, Jackson E [VerfasserIn] |
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| Links: |
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| Themen: |
Aging |
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| Anmerkungen: |
Date Completed 12.03.2024 Date Revised 13.03.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1042/BCJ20230421 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM36880920X |
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| 245 | 1 | 0 | |a Cardiomyocyte-specific deletion of GCN5L1 reduces lysine acetylation and attenuates diastolic dysfunction in aged mice by improving cardiac fatty acid oxidation |
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| 520 | |a © 2024 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society. | ||
| 520 | |a Cardiac mitochondrial dysfunction is a critical contributor to the pathogenesis of aging and many age-related conditions. As such, complete control of mitochondrial function is critical to maintain cardiac efficiency in the aged heart. Lysine acetylation is a reversible post-translational modification shown to regulate several mitochondrial metabolic and biochemical processes. In the present study, we investigated how mitochondrial lysine acetylation regulates fatty acid oxidation (FAO) and cardiac function in the aged heart. We found a significant increase in mitochondrial protein acetylation in the aged heart which correlated with increased level of mitochondrial acetyltransferase-related protein GCN5L1. We showed that acetylation status of several fatty acid and glucose oxidation enzymes (long-chain acyl-coenzyme A dehydrogenase, hydroxyacyl-coA dehydrogenase, and pyruvate dehydrogenase) were significantly up-regulated in aged heart which correlated with decreased enzymatic activities. Using a cardiac-specific GCN5L1 knockout (KO) animal model, we showed that overall acetylation of mitochondrial proteins was decreased in aged KO animals, including FAO proteins which led to improved FAO activity and attenuated cardiac diastolic dysfunction observed in the aged heart. Together, these findings indicate that lysine acetylation regulates FAO in the aged heart which results in improved cardiac diastolic function and this is in part regulated by GCN5L1 | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Stoner, Michael W |e verfasserin |4 aut | |
| 700 | 1 | |a Scott, Iain |e verfasserin |4 aut | |
| 700 | 1 | |a Thapa, Dharendra |e verfasserin |4 aut | |
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