NAD+ is a vital molecule in cellular redox reactions and acts as a cosubstrate for NAD+ consuming enzymes, which are critical to a variety of biological processes. In C. elegans, NAD+ salvage biosynthesis recycles the nicotinamide (NAM) liberated by NAD+ consumers to rebuild the NAD+ reservoir.
pnc-1 is a nicotinamidase in the NAD+ salvage pathway. It catalyzes the deamination of NAM to nicotinic acid (NA). Our previous studies have shown that NAD+ biosynthesis contributes to the development and function to multiple muscle types in C. elegans. We have also found muscle type-specific response to perturbations of NAD+ or NAM levels [1]. Muscle is a major energy consuming tissue, and NAD+ is actively involved in ATP production. Moreover, there is accumulating data on the regulatory roles of the NAD+ consumer sirtuins in metabolism [2]. Thus we hypothesized that the
pnc-1 mutants may be defective in energy production and/or storage. To address this hypothesis, we treated wild type and
pnc-1 mutant with sodium azide, which inhibits complex IV of the electron transport chain. We found that the
pnc-1 mutant paralyzes faster than wild type upon azide treatment. After removing the worms from azide,
pnc-1 mutants took longer than wild type to begin to recover from paralysis but then recovered to a full muscle capacity at the same rate as wild type. Our observation indicates that
pnc-1 mutant is sensitive to ATP depletion, and is slow in recovery of ATP production. We also examined fat storage in wild type,
pnc-1 mutant and
pnc-1 over-expression strains. At young adult stage, the
pnc-1 mutant stores more fat than wild type, and the
pnc-1 over-expression strain stores less fat than wild type. Thus NAD+ salvage biosynthesis regulates fat metabolism, which contributes to energy production and storage.
[1]Vrablik, T. L., Wang, W., Upadhyay, A. and Hanna-Rose, W. (2011). "Muscle type-specific responses to NAD+ salvage biosynthesis promote muscle function in Caenorhabditis elegans." Dev Biol. 15;349(2):387-94.
[2]Imai, S. and Guarente, L. (2010). "Ten years of NAD-dependent SIR2 family deacetylases: implications for metabolic diseases." Trends Pharmacol Sci 31(5): 212-20.