MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD+ consumption.
Histone variants are structural components of eukaryotic chromatin that can replace replication-coupled histones in the nucleosome. The histone variant macroH2A1.1 contains a macrodomain capable of binding NAD+-derived metabolites. Here we report that macroH2A1.1 is rapidly induced during myogenic d...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Nature Publishing Group
2017
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| _version_ | 1797075230770855936 |
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| author | Marjanović, M Hurtado-Bagès, S Lassi, M Valero, V Malinverni, R Delage, H Navarro, M Corujo, D Guberovic, I Douet, J Gama-Perez, P Garcia-Roves, P Ahel, I Ladurner, A Yanes, O Bouvet, P Suelves, M Teperino, R Pospisilik, J Buschbeck, M |
| author_facet | Marjanović, M Hurtado-Bagès, S Lassi, M Valero, V Malinverni, R Delage, H Navarro, M Corujo, D Guberovic, I Douet, J Gama-Perez, P Garcia-Roves, P Ahel, I Ladurner, A Yanes, O Bouvet, P Suelves, M Teperino, R Pospisilik, J Buschbeck, M |
| author_sort | Marjanović, M |
| collection | OXFORD |
| description | Histone variants are structural components of eukaryotic chromatin that can replace replication-coupled histones in the nucleosome. The histone variant macroH2A1.1 contains a macrodomain capable of binding NAD+-derived metabolites. Here we report that macroH2A1.1 is rapidly induced during myogenic differentiation through a switch in alternative splicing, and that myotubes that lack macroH2A1.1 have a defect in mitochondrial respiratory capacity. We found that the metabolite-binding macrodomain was essential for sustained optimal mitochondrial function but dispensable for gene regulation. Through direct binding, macroH2A1.1 inhibits basal poly-ADP ribose polymerase 1 (PARP-1) activity and thus reduces nuclear NAD+ consumption. The resultant accumulation of the NAD+ precursor NMN allows for maintenance of mitochondrial NAD+ pools that are critical for respiration. Our data indicate that macroH2A1.1-containing chromatin regulates mitochondrial respiration by limiting nuclear NAD+ consumption and establishing a buffer of NAD+ precursors in differentiated cells. |
| first_indexed | 2024-03-06T23:47:29Z |
| format | Journal article |
| id | oxford-uuid:71710a27-1c31-4e05-89ec-e82a18e9465e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:47:29Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:71710a27-1c31-4e05-89ec-e82a18e9465e2022-03-26T19:43:43ZMacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD+ consumption.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:71710a27-1c31-4e05-89ec-e82a18e9465eEnglishSymplectic Elements at OxfordNature Publishing Group2017Marjanović, MHurtado-Bagès, SLassi, MValero, VMalinverni, RDelage, HNavarro, MCorujo, DGuberovic, IDouet, JGama-Perez, PGarcia-Roves, PAhel, ILadurner, AYanes, OBouvet, PSuelves, MTeperino, RPospisilik, JBuschbeck, MHistone variants are structural components of eukaryotic chromatin that can replace replication-coupled histones in the nucleosome. The histone variant macroH2A1.1 contains a macrodomain capable of binding NAD+-derived metabolites. Here we report that macroH2A1.1 is rapidly induced during myogenic differentiation through a switch in alternative splicing, and that myotubes that lack macroH2A1.1 have a defect in mitochondrial respiratory capacity. We found that the metabolite-binding macrodomain was essential for sustained optimal mitochondrial function but dispensable for gene regulation. Through direct binding, macroH2A1.1 inhibits basal poly-ADP ribose polymerase 1 (PARP-1) activity and thus reduces nuclear NAD+ consumption. The resultant accumulation of the NAD+ precursor NMN allows for maintenance of mitochondrial NAD+ pools that are critical for respiration. Our data indicate that macroH2A1.1-containing chromatin regulates mitochondrial respiration by limiting nuclear NAD+ consumption and establishing a buffer of NAD+ precursors in differentiated cells. |
| spellingShingle | Marjanović, M Hurtado-Bagès, S Lassi, M Valero, V Malinverni, R Delage, H Navarro, M Corujo, D Guberovic, I Douet, J Gama-Perez, P Garcia-Roves, P Ahel, I Ladurner, A Yanes, O Bouvet, P Suelves, M Teperino, R Pospisilik, J Buschbeck, M MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD+ consumption. |
| title | MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD+ consumption. |
| title_full | MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD+ consumption. |
| title_fullStr | MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD+ consumption. |
| title_full_unstemmed | MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD+ consumption. |
| title_short | MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD+ consumption. |
| title_sort | macroh2a1 1 regulates mitochondrial respiration by limiting nuclear nad consumption |
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