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    Nicotinamide mononucleotide alters mitochondrial dynamics by SIRT3-dependent mechanism in male mice

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    Author
    Klimova, N.
    Long, A.
    Kristian, T.
    Date
    2019
    Journal
    Journal of Neuroscience Research
    Publisher
    John Wiley and Sons Inc.
    Type
    article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1002/jnr.24397
    Abstract
    Nicotinamide adenine dinucleotide (NAD+) is a central signaling molecule and enzyme cofactor that is involved in a variety of fundamental biological processes. NAD+ levels decline with age, neurodegenerative conditions, acute brain injury, and in obesity or diabetes. Loss of NAD+ results in impaired mitochondrial and cellular functions. Administration of NAD+ precursor, nicotinamide mononucleotide (NMN), has shown to improve mitochondrial bioenergetics, reverse age‐associated physiological decline, and inhibit postischemic NAD+ degradation and cellular death. In this study, we identified a novel link between NAD+ metabolism and mitochondrial dynamics. A single dose (62.5 mg/kg) of NMN, administered to male mice, increases hippocampal mitochondria NAD+ pools for up to 24 hr posttreatment and drives a sirtuin 3 (SIRT3)‐mediated global decrease in mitochondrial protein acetylation. This results in a reduction of hippocampal reactive oxygen species levels via SIRT3‐driven deacetylation of mitochondrial manganese superoxide dismutase. Consequently, mitochondria in neurons become less fragmented due to lower interaction of phosphorylated fission protein, dynamin‐related protein 1 (pDrp1 [S616]), with mitochondria. In conclusion, manipulation of mitochondrial NAD+ levels by NMN results in metabolic changes that protect mitochondria against reactive oxygen species and excessive fragmentation, offering therapeutic approaches for pathophysiologic stress conditions.
    Sponsors
    This work was supported by U.S. Veterans Affairs Merit grant BX000917 to TK.
    Keyword
    brain
    dynamin-1-like protein
    mitochondria
    mitochondrial dynamics
    nicotinamide adenine dinucleotide
    nicotinamide mononucleotide
    ROS (reactive oxygen species)
    sirtuin 3
    superoxide dismutase
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85060355005&doi=10.1002%2fjnr.24397&partnerID=40&md5=1687494c4cab8a2e4678942113ff7cbe; http://hdl.handle.net/10713/10191
    ae974a485f413a2113503eed53cd6c53
    10.1002/jnr.24397
    Scopus Count
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    UMB Open Access Articles 2019

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