# name
MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD+ consumption

# metadata.dc.description.abstract[].value
Histone variants are structural components of eukaryotic chromatin that can replace replication-coupled histones in the nucleosome. The histone variant macroH2A.1.1 contains a macrodomain able to bind NAD+ derived metabolites. Here, we report that macroH2A.1.1 is rapidly induced during myogenic differentiation through a switch in alternative splicing. Importantly, myotubes lacking macroH2A.1.1 display a defect in mitochondrial respiratory capacity. We find that the metabolite-interacting macrodomain is essential for sustaining optimal mitochondrial function, but dispensable for gene regulation. Through direct binding, macroH2A.1.1 inhibits basal poly-ADP ribose polymerase 1 activity and thus reduces nuclear NAD+ consumption. Consequentially, accumulation of the NAD+ precursor NMN allows the maintenance of mitochondrial NAD+ pools critical for respiration. Our data indicate that macroH2A.1.1-containing chromatin regulates mitochondrial respiration by limiting nuclear NAD+ consumption and establishing a buffer of NAD+ precursors in differentiated cells.

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Nature Structural & Molecular Biology, 2017, vol. 24, num. 11, p. 902-910

# metadata.dc.rights[].value
(c) Marjanovic, Melanija Posavec et al., 2017

# metadata.dc.source[].value
Articles publicats en revistes (Ciències Fisiològiques)

# metadata.dc.title[].value
MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD+ consumption