title: Life-span extension by a metacaspase in the yeast Saccharomyces cerevisiae.
abstract: Single-cell species harbor ancestral structural homologs of caspase proteases, although the evolutionary benefit of such apoptosis-related proteins in unicellular organisms is unclear. Here, we found that the yeast metacaspase Mca1 is recruited to the insoluble protein deposit (IPOD) and juxtanuclear quality-control compartment (JUNQ) during aging and proteostatic stress. Elevating MCA1 expression counteracted accumulation of unfolded proteins and aggregates and extended life span in a heat shock protein Hsp104 disaggregase- and proteasome-dependent manner. Consistent with a role in protein quality control, genetic interaction analysis revealed that MCA1 buffers against deficiencies in the Hsp40 chaperone YDJ1 in a caspase cysteine-dependent manner. Life-span extension and aggregate management by Mca1 was only partly dependent on its conserved catalytic cysteine, which suggests that Mca1 harbors both caspase-dependent and independent functions related to life-span control.
authors.affiliation: Department of Chemistry and Molecular Biology (CMB), University of Gothenburg, Medicinaregatan 9C, S-413 90 Göteborg, Sweden.
authors.forename: Sandra Malmgren
authors.initials: SM
authors.lastname: Hill
authors.affiliation: Department of Chemistry and Molecular Biology (CMB), University of Gothenburg, Medicinaregatan 9C, S-413 90 Göteborg, Sweden.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Hao
authors.affiliation: Department of Chemistry and Molecular Biology (CMB), University of Gothenburg, Medicinaregatan 9C, S-413 90 Göteborg, Sweden. thomas.nystrom@cmb.gu.se beidong.liu@cmb.gu.se.
authors.forename: Beidong
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Chemistry and Molecular Biology (CMB), University of Gothenburg, Medicinaregatan 9C, S-413 90 Göteborg, Sweden. thomas.nystrom@cmb.gu.se beidong.liu@cmb.gu.se.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nyström
mesh_terms: D017209:Apoptosis; D020169:Caspases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002384:Catalysis; D020134:Catalytic Domain; D017124:Conserved Sequence; D003545:Cysteine / Q000737:chemistry / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D008136:Longevity; D021381:Protein Transport; D059748:Proteolysis; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D056811:Unfolded Protein Response
chemical_list: D006360:Heat-Shock Proteins; D029701:Saccharomyces cerevisiae Proteins; C070972:HsP104 protein, S cerevisiae; D020169:Caspases; C456272:MCA1 protein, S cerevisiae; D003545:Cysteine