Title:
Role of NAD metabolism in aging and diseases

 

Speaker:
Takashi Nakagawa
Department of Metabolism and Nutrition, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama

 

Abstract:
Nicotinamide adenine dinucleotide (NAD) is an essential co-factor mediating numbers of metabolic enzymatic reactions. NAD also serves as a substrate for poly (ADP-Ribose) polymerases (PARPs) and NAD-dependent deacetylases (Sirtuins), and plays key roles in many cellular processes. Particularly, sirtuins are well known aaging related molecule. Therefore, it is considered that intracellular NAD level critically regulates wide range of cellular functions in response to nutrient conditions, and ultimately governs aging process. In organisms, NAD can be synthesized by de novo and salvage pathways. In salvage pathway, nicotinamide (NAM) is converted to nicotinamide mononucleotide (NMN) by Nampt (Nicotinamide phosphoribosyl- transferase), and then nicotinamide mononucleotide adenylyltransferase (Nmnat) generates NAD from NMN. In mammals, there are three isoforms of Nmnat, and they are localized in different cellular compartments. Nmnat3 is believed to be localized in mitochondria and considered to have a pivotal role in the regulation of mitochondrial NAD level. Despite of the importance of NAD metabolism in mitochondria, the role of Nmnat3 in vivo is still unclear. To investigate the physiological role of Nmnat3, we generated Nmnat3 deficient mice. Interestingly, Nmnat3 deficient mice exhibit splenomegaly and hemolytic anemia. To elucidate the further mechanism how Nmnat3 deficiency leads to hemolytic anemia, we employed metabolomics analysis by LC-MS and found that some important metabolic pathways were altered in Nmnat3 deficient mice. In this seminar, I will present our recent data obtained from the analysis of Nmnat3 deficient and Tg mice and will discuss about role of NAD metabolism in aging and diseases.

 

References:
1)Cancer Metastasis Review. doi: 10.1007/s10555-017-9691-z. (2017)
2)PLOS ONE 11(1): e0147037. (2016)
3)J Biol Chem. 289(21): 14796-14811. (2014)