Less is more: Nutrient limitation induces cross-talk of nutrient sensing pathways with NAD+homeostasis and contributes to longevity.
Nutrient sensing pathways and their regulation grant cells control over their metabolism and growth in response to changing nutrients. Factors that regulate nutrient sensing can also modulate longevity. Reduced activity of nutrient sensing pathways such as glucose-sensing PKA, nitrogen-sensing TOR and S6 kinase homolog Sch9 have been linked to increased life span in the yeast,Saccharomyces cerevisiae, and higher eukaryotes. Recently, reduced activity of amino acid sensing SPS pathway was also shown to increase yeast life span. Life span extension by reduced SPS activity requires enhanced NAD+(nicotinamide adenine dinucleotide, oxidized form) and nicotinamide riboside (NR, a NAD+precursor) homeostasis. Maintaining adequate NAD+pools has been shown to play key roles in life span extension, but factors regulating NAD+metabolism and homeostasis are not completely understood. Recently, NAD+metabolism was also linked to the phosphate (Pi)-sensingPHOpathway in yeast. CanonicalPHOactivation requires Pi-starvation. Interestingly, NAD+depletion without Pi-starvation was sufficient to inducePHOactivation, increasing NR production and mobilization. Moreover, SPS signaling appears to function in parallel withPHOsignaling components to regulate NR/NAD+homeostasis. These studies suggest that NAD+metabolism is likely controlled by and/or coordinated with multiple nutrient sensing pathways. Indeed, cross-regulation ofPHO, PKA, TOR and Sch9 pathways was reported to potentially affect NAD+metabolism; though detailed mechanisms remain unclear. This review discusses yeast longevity-related nutrient sensing pathways and possible mechanisms of life span extension, regulation of NAD+homeostasis, and cross-talk among nutrient sensing pathways and NAD+homeostasis.
Department of Microbiology and Molecular Genetics, College of Biological Sciences, University of California, Davis, CA 95616, USA.
Felicia
F
Tsang
Department of Microbiology and Molecular Genetics, College of Biological Sciences, University of California, Davis, CA 95616, USA.
Su-Ju
SJ
Lin
NAD+ homeostasis; Nutrient sensing; yeast longevity
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