title: L-carnosine affects the growth of Saccharomyces cerevisiae in a metabolism-dependent manner.
abstract: The dipeptide L-carnosine (β-alanyl-L-histidine) has been described as enigmatic: it inhibits growth of cancer cells but delays senescence in cultured human fibroblasts and extends the lifespan of male fruit flies. In an attempt to understand these observations, the effects of L-carnosine on the model eukaryote, Saccharomyces cerevisiae, were examined on account of its unique metabolic properties; S. cerevisiae can respire aerobically, but like some tumor cells, it can also exhibit a metabolism in which aerobic respiration is down regulated. L-Carnosine exhibited both inhibitory and stimulatory effects on yeast cells, dependent upon the carbon source in the growth medium. When yeast cells were not reliant on oxidative phosphorylation for energy generation (e.g. when grown on a fermentable carbon source such as 2% glucose), 10-30 mM L-carnosine slowed growth rates in a dose-dependent manner and increased cell death by up to 17%. In contrast, in media containing a non-fermentable carbon source in which yeast are dependent on aerobic respiration (e.g. 2% glycerol), L-carnosine did not provoke cell death. This latter observation was confirmed in the respiratory yeast, Pichia pastoris. Moreover, when deletion strains in the yeast nutrient-sensing pathway were treated with L-carnosine, the cells showed resistance to its inhibitory effects. These findings suggest that L-carnosine affects cells in a metabolism-dependent manner and provide a rationale for its effects on different cell types.
authors.affiliation: Aston Research Centre for Healthy Ageing, School of Health and Life Sciences, Aston University, Birmingham, United Kingdom.
authors.forename: Stephanie P
authors.initials: SP
authors.lastname: Cartwright
authors.forename: Roslyn M
authors.initials: RM
authors.lastname: Bill
authors.forename: Alan R
authors.initials: AR
authors.lastname: Hipkiss
mesh_terms: D002151:Calorimetry / Q000379:methods; D002331:Carnitine / Q000494:pharmacology*; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D025141:Drug Resistance, Fungal / Q000235:genetics; D005947:Glucose / Q000494:pharmacology; D005990:Glycerol / Q000494:pharmacology; D050296:Microbial Viability / Q000187:drug effects* / Q000235:genetics; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D014803:Vitamin B Complex / Q000494:pharmacology
chemical_list: D002331:Carnitine; D003470:Culture Media; D005947:Glucose; D005990:Glycerol; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D029701:Saccharomyces cerevisiae Proteins; D014803:Vitamin B Complex; C083324:TOR1 protein, S cerevisiae; C530964:SCH9 protein, S cerevisiae