Author, as appears in the article.: 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;
Department: Enginyeria Electrònica, Elèctrica i Automàtica
URV's Author/s: Yanes Torrado, Óscar
Keywords: Hashtag Etiqueta «#» @uroweb @residentesaeu @infoAeu
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.
Thematic Areas: Structural biology Molecular biology Medicina ii General medicine Engenharias iv Ciências biológicas i Cell biology Biophysics Biochemistry & molecular biology
licence for use: https://creativecommons.org/licenses/by/3.0/es/
ISSN: 15459985
Author's mail: oscar.yanes@urv.cat
Author identifier: 0000-0003-3695-7157
Record's date: 2024-09-07
Papper version: info:eu-repo/semantics/acceptedVersion
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Nature Structural & Molecular Biology. 24 (11): 902-+
APA: Marjanovic, Melanija Posavec; Hurtado-Bages, Sarah; Lassi, Maximilian; Valero, Vanesa; Malinverni, Roberto; Delage, Helene; Navarro, Miriam; Corujo, D (2017). MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD(+) consumption. Nature Structural & Molecular Biology, 24(11), 902-+. DOI: 10.1038/nsmb.3481
Entity: Universitat Rovira i Virgili
Journal publication year: 2017
Publication Type: Journal Publications
Repositori URV