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  MacroH2A1.1 regualtes mitochondrial respiration by limiting nuelcear NAD+ consumption

Marjanović, M. P., Hurtado-Bagès, S., Lassi, M., Valero, V., Malinverni, R., Delage, H., et al. (2017). MacroH2A1.1 regualtes mitochondrial respiration by limiting nuelcear NAD+ consumption. Nature Structural and Molecular Biology, 902-910. doi:10.1038/nsmb.3481.

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Item Permalink: https://hdl.handle.net/21.11116/0000-0000-AF46-D Version Permalink: https://hdl.handle.net/21.11116/0000-0000-AF47-C
Genre: Journal Article

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 Creators:
Marjanović, Melanija Posavec1, Author
Hurtado-Bagès, Sarah1, Author
Lassi, Maximilian1, Author
Valero, Vanesa1, Author
Malinverni, Roberto1, Author
Delage, Hélène1, Author
Navarro, Miriam1, Author
Corujo, David1, Author
Guberovic, Iva1, Author
Douet, Julien1, Author
Gama-Perez, Pau1, Author
Garcia-Roves, Pablo M1, Author
Ahel, Ivan1, Author
Ladurner, Andreas G1, Author
Yanes, Oscar1, Author
Bouvet, Philippe1, Author
Suelves, Mònica1, Author
Teperino, Raffaele2, Author
Pospisilik, J Andrew2, Author
Buschbeck, Marcus1, Author
Affiliations:
1External Organizations, ou_persistent22              
2Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, 79108 Freiburg, DE, ou_2243640              

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 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.

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Language(s): eng - English
 Dates: 2017-11
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1038/nsmb.3481
 Degree: -

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Title: Nature Structural and Molecular Biology
  Other : Nature Struct Biol
Source Genre: Journal
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Publ. Info: New York, NY : Nature Pub. Group
Pages: - Volume / Issue: - Sequence Number: - Start / End Page: 902 - 910 Identifier: ISSN: 1545-9993
CoNE: https://pure.mpg.de/cone/journals/resource/954925603763