title: Tor1 regulates protein solubility in Saccharomyces cerevisiae.
abstract: Accumulation of insoluble protein in cells is associated with aging and aging-related diseases; however, the roles of insoluble protein in these processes are uncertain. The nature and impact of changes to protein solubility during normal aging are less well understood. Using quantitative mass spectrometry, we identify 480 proteins that become insoluble during postmitotic aging in Saccharomyces cerevisiae and show that this ensemble of insoluble proteins is similar to those that accumulate in aging nematodes. SDS-insoluble protein is present exclusively in a nonquiescent subpopulation of postmitotic cells, indicating an asymmetrical distribution of this protein. In addition, we show that nitrogen starvation of young cells is sufficient to cause accumulation of a similar group of insoluble proteins. Although many of the insoluble proteins identified are known to be autophagic substrates, induction of macroautophagy is not required for insoluble protein formation. However, genetic or chemical inhibition of the Tor1 kinase is sufficient to promote accumulation of insoluble protein. We conclude that target of rapamycin complex 1 regulates accumulation of insoluble proteins via mechanisms acting upstream of macroautophagy. Our data indicate that the accumulation of proteins in an SDS-insoluble state in postmitotic cells represents a novel autophagic cargo preparation process that is regulated by the Tor1 kinase.
authors.affiliation: The Buck Institute for Research on Aging, Novato, CA 94945, USA.
authors.forename: Theodore W
authors.initials: TW
authors.lastname: Peters
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Rardin
authors.forename: Gregg
authors.initials: G
authors.lastname: Czerwieniec
authors.forename: Uday S
authors.initials: US
authors.lastname: Evani
authors.forename: Pedro
authors.initials: P
authors.lastname: Reis-Rodrigues
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Lithgow
authors.forename: Sean D
authors.initials: SD
authors.lastname: Mooney
authors.forename: Bradford W
authors.initials: BW
authors.lastname: Gibson
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hughes
mesh_terms: D001343:Autophagy; D000071193:Autophagy-Related Protein 7; D000071183:Autophagy-Related Proteins; D004591:Electrophoresis, Polyacrylamide Gel; D013058:Mass Spectrometry; D000076222:Mechanistic Target of Rapamycin Complex 1; D008938:Mitosis; D046912:Multiprotein Complexes / Q000378:metabolism; D009154:Mutation; D009584:Nitrogen / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D012995:Solubility; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013997:Time Factors
chemical_list: D000071193:Autophagy-Related Protein 7; D000071183:Autophagy-Related Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D009584:Nitrogen; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D029701:Saccharomyces cerevisiae Proteins; D012967:Sodium Dodecyl Sulfate; D058570:TOR Serine-Threonine Kinases; C114830:ATG7 protein, S cerevisiae; C477823:ATG1 protein, S cerevisiae; C083324:TOR1 protein, S cerevisiae