Marjanovic, Melanija Posavec; Hurtado-Bages, Sarah; Lassi, Maximilian; Valero, Vanesa; Malinverni, Roberto; Delage, Helene; Navarro, Miriam; Corujo, David; Guberovic, Iva; Douet, Julien; Gama-Perez, Pau; Garcia-Roves, Pablo M.; Ahel, Ivan; Ladurner, Andreas G.; Yanes, Oscar; Bouvet, Philippe; Suelves, Monica; Teperino, Raffaele; Pospisilik, J. Andrew; Buschbeck, Marcus (2017): MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD(+) consumption. In: Nature Structural & Molecular Biology, Vol. 24, No. 11: pp. 902-910 |
Abstract
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.
Item Type: | Journal article |
---|---|
Faculties: | Medicine |
Subjects: | 600 Technology > 610 Medicine and health |
ISSN: | 1545-9993 |
Language: | English |
ID Code: | 52423 |
Deposited On: | 14. Jun 2018 09:50 |
Last Modified: | 04. Nov 2020 13:31 |
- BASE
- Marjanovic, Melanija Posavec
- Hurtado-Bages, Sarah
- Lassi, Maximilian
- Valero, Vanesa
- Malinverni, Roberto
- Delage, Helene
- Navarro, Miriam
- Corujo, David
- Guberovic, Iva
- Douet, Julien
- Gama-Perez, Pau
- Garcia-Roves, Pablo M.
- Ahel, Ivan
- Ladurner, Andreas G.
- Yanes, Oscar
- Bouvet, Philippe
- Suelves, Monica
- Teperino, Raffaele
- Pospisilik, J. Andrew
- Buschbeck, Marcus
- Google Scholar
- Marjanovic, Melanija Posavec
- Hurtado-Bages, Sarah
- Lassi, Maximilian
- Valero, Vanesa
- Malinverni, Roberto
- Delage, Helene
- Navarro, Miriam
- Corujo, David
- Guberovic, Iva
- Douet, Julien
- Gama-Perez, Pau
- Garcia-Roves, Pablo M.
- Ahel, Ivan
- Ladurner, Andreas G.
- Yanes, Oscar
- Bouvet, Philippe
- Suelves, Monica
- Teperino, Raffaele
- Pospisilik, J. Andrew
- Buschbeck, Marcus