title: Quantitative Global Proteomics of Yeast PBP1 Deletion Mutants and Their Stress Responses Identifies Glucose Metabolism, Mitochondrial, and Stress Granule Changes.
abstract: The yeast protein PBP1 is implicated in very diverse pathways. Intriguingly, its deletion mitigates the toxicity of human neurodegeneration factors. Here, we performed label-free quantitative global proteomics to identify crucial downstream factors, either without stress or under cell stress conditions (heat and NaN3). Compared to the wildtype BY4741 strain, PBP1 deletion always triggered downregulation of the key bioenergetics enzyme KGD2 and the prion protein RNQ1 as well as upregulation of the leucine biosynthesis enzyme LEU1. Without stress, enrichment of stress response factors was consistently detected for both deletion mutants; upon stress, these factors were more pronounced. The selective analysis of components of stress granules and P-bodies revealed a prominent downregulation of GIS2. Our yeast data are in good agreement with a global proteomics and metabolomics publication that the PBP1 ortholog ATAXIN-2 (ATXN2) knockout (KO) in mouse results in mitochondrial deficits in leucine/fatty acid catabolism and bioenergetics, with an obesity phenotype. Furthermore, our data provide the completely novel insight that PBP1 mutations in stress periods involve GIS2, a plausible scenario in view of previous data that both PBP1 and GIS2 relocalize from ribosomes to stress granules, interact with poly(A)-binding protein in translation regulation and prevent mitochondrial precursor overaccumulation stress (mPOS). This may be relevant for human diseases like spinocerebellar ataxias, amyotrophic lateral sclerosis, and the metabolic syndrome.
authors.affiliation: Max Planck Institute for Molecular Genetics, Ihnestraße 63-73, 14195 Berlin, Germany.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Seidel
authors.affiliation: Max Planck Institute for Molecular Genetics, Ihnestraße 63-73, 14195 Berlin, Germany.
authors.forename: David
authors.identifier: 0000-0002-0170-868X
authors.initials: D
authors.lastname: Meierhofer
authors.affiliation: Experimental Neurology, Goethe University Medical School , Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany.
authors.forename: Nesli-Ece
authors.initials: NE
authors.lastname: Şen
authors.affiliation: Max Planck Institute for Molecular Genetics, Ihnestraße 63-73, 14195 Berlin, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Guenther
authors.affiliation: Max Planck Institute for Molecular Genetics, Ihnestraße 63-73, 14195 Berlin, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Krobitsch
authors.affiliation: Experimental Neurology, Goethe University Medical School , Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Auburger
mesh_terms: D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D006358:Hot Temperature; D006836:Hydro-Lyases / Q000235:genetics / Q000378:metabolism; D007655:Ketoglutarate Dehydrogenase Complex / Q000235:genetics / Q000378:metabolism; D011328:Prions / Q000235:genetics / Q000378:metabolism; D020543:Proteome / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D019810:Sodium Azide / Q000494:pharmacology; D013312:Stress, Physiological
chemical_list: D002352:Carrier Proteins; C557900:Gis2 protein, S cerevisiae; C116076:PBP1 protein, S cerevisiae; D011328:Prions; D020543:Proteome; D016601:RNA-Binding Proteins; C404807:RNQ1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D019810:Sodium Azide; D007655:Ketoglutarate Dehydrogenase Complex; D006836:Hydro-Lyases; C021455:3-isopropylmalate dehydratase
keywords: PBP1; mass spectrometry; neurobiology; proteome profiling; stress response