| First Author | Klimova N | Year | 2019 |
| Journal | J Neurosci Res | Volume | 97 |
| Issue | 8 | Pages | 975-990 |
| PubMed ID | 30801823 | Mgi Jnum | J:286173 |
| Mgi Id | MGI:6390469 | Doi | 10.1002/jnr.24397 |
| Citation | Klimova N, et al. (2019) Nicotinamide mononucleotide alters mitochondrial dynamics by SIRT3-dependent mechanism in male mice. J Neurosci Res 97(8):975-990 |
| abstractText | 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. |
