title: Genetic manipulation of longevity-related genes as a tool to regulate yeast life span and metabolite production during winemaking.
abstract: BACKGROUND
  Yeast viability and vitality are essential for different industrial processes where the yeast Saccharomyces cerevisiae is used as a biotechnological tool. Therefore, the decline of yeast biological functions during aging may compromise their successful biotechnological use. Life span is controlled by a variety of molecular mechanisms, many of which are connected to stress tolerance and genomic stability, although the metabolic status of a cell has proven a main factor affecting its longevity. Acetic acid and ethanol accumulation shorten chronological life span (CLS), while glycerol extends it.
  
  
  RESULTS
  Different age-related gene classes have been modified by deletion or overexpression to test their role in longevity and metabolism. Overexpression of histone deacetylase SIR2 extends CLS and reduces acetate production, while overexpression of SIR2 homolog HST3 shortens CLS, increases the ethanol level, and reduces acetic acid production. HST3 overexpression also enhances ethanol tolerance. Increasing tolerance to oxidative stress by superoxide dismutase SOD2 overexpression has only a moderate positive effect on CLS. CLS during grape juice fermentation has also been studied for mutants on several mRNA binding proteins that are regulators of gene expression at the posttranscriptional level; we found that NGR1 and UTH4 deletions decrease CLS, while PUF3 and PUB1 deletions increase it. Besides, the pub1Δ mutation increases glycerol production and blocks stress granule formation during grape juice fermentation. Surprisingly, factors relating to apoptosis, such as caspase Yca1 or apoptosis-inducing factor Aif1, play a positive role in yeast longevity during winemaking as their deletions shorten CLS.
  
  
  CONCLUSIONS
  Manipulation of regulators of gene expression at both transcriptional (i.e., sirtuins) and posttranscriptional (i.e., mRNA binding protein Pub1) levels allows to modulate yeast life span during its biotechnological use. Due to links between aging and metabolism, it also influences the production profile of metabolites of industrial relevance.
authors.affiliation: Departamento de Biotecnología, Instituto de Agroquímica y Tecnología de Alimentos-CSIC, Av, Agustín Escardino, 7, Paterna 46980, Spain.
authors.forename: Helena
authors.initials: H
authors.lastname: Orozco
authors.forename: Emilia
authors.initials: E
authors.lastname: Matallana
authors.forename: Agustín
authors.initials: A
authors.lastname: Aranda
mesh_terms: D019342:Acetic Acid / Q000378:metabolism; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism; D005285:Fermentation; D017353:Gene Deletion; D005990:Glycerol / Q000378:metabolism; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D008136:Longevity / Q000235:genetics*; D009154:Mutation; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D056565:Sirtuin 2 / Q000235:genetics / Q000378:metabolism; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014920:Wine / Q000382:microbiology*; D000099156:Superoxide Dismutase 2
chemical_list: D019342:Acetic Acid; D020169:Caspases; D000431:Ethanol; D005990:Glycerol; D006655:Histone Deacetylases; D009247:NADH, NADPH Oxidoreductases; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C443623:AIF1 protein, S cerevisiae; C456272:MCA1 protein, S cerevisiae; C512517:Hst3 protein, S cerevisiae; C087778:SIR2 protein, S cerevisiae