The co-enzyme nicotinamide adenine dinucleotide (NAD+) is found in all living cells and serves as an electron shuttle. NAD+consumer enzymes hydrolyse NAD+ to nicotinamide; this is recycled to NAD+ via the NAD+ salvage pathway, which differs between vertebrates and invertebrates. Now, on , Wendy Hanna-Rose and colleagues reveal, for the first time, a developmental role for components of this well-studied pathway. They show that the C. elegans nicotinamidase PNC-1, the first enzyme in the worm NAD+ salvage pathway, is required for normal reproductive development, with pnc-1 mutant animals showing delayed gonad development and egg-laying defects. Interestingly, the gonad defects are caused by the lack of NAD+, but the egg-laying defects by nicotinamide accumulation, indicating that both substrate and product levels are important biologically. Furthermore, the researchers find that the mouse functional equivalent of PNC in the NAD+ salvage pathway, Nampt,can rescue pnc-1 mutants. Together, these findings indicate for the first time that NAD+ salvage pathway components might have evolutionarily conserved developmental functions.
