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

Journal of Neuroscience Research
Nina KlimovaTibor Kristian

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, man...Continue Reading

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Citations

Jan 21, 2019·Neurochemical Research·Nina Klimova, Tibor Kristian
Jul 1, 2020·Antioxidants & Redox Signaling·Gayle M GordilloChandan K Sen
May 16, 2020·Frontiers in Cell and Developmental Biology·Weiqi HongXiawei Wei
Jan 10, 2020·Experimental Gerontology·Nady Braidy, Yue Liu
Apr 13, 2021·Expert Opinion on Therapeutic Targets·Fabio Coppedè
Jul 25, 2021·Mechanisms of Ageing and Development·Catherine Li, Lindsay E Wu
Nov 24, 2021·Biochemical Society Transactions·Golam M UddinTimothy E Shutt

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