title: Aging and calorie restriction modulate yeast redox state, oxidized protein removal, and the ubiquitin-proteasome system.
abstract: The ubiquitin-proteasome system governs the half-life of most cellular proteins. Calorie restriction (CR) extends the maximum life span of a variety of species and prevents oxidized protein accumulation. We studied the effects of CR on the ubiquitin-proteasome system and protein turnover in aging Saccharomyces cerevisiae. CR increased chronological life span as well as proteasome activity compared to control cells. The levels of protein carbonyls, a marker of protein oxidation, and those of polyubiquitinated proteins were modulated by CR. Controls, but not CR cells, exhibited a significant increase in oxidized proteins. In keeping with decreased proteasome activity, polyubiquitinated proteins were increased in young control cells compared to time-matched CR cells, but were profoundly decreased in aged control cells despite decreased proteasomal activity. This finding is related to a decreased polyubiquitination ability due to the impairment of the ubiquitin-activating enzyme in aged control cells, probably related to a more oxidative microenvironment. CR preserves the ubiquitin-proteasome system activity. Overall, we found that aging and CR modulate many aspects of protein modification and turnover.
authors.affiliation: Departamento de Bioquímica, Universidade de São Paulo, 05508-900 Cidade Universitária, São Paulo, Brazil.
authors.forename: Fernanda Marques
authors.initials: FM
authors.lastname: da Cunha
authors.forename: Marilene
authors.initials: M
authors.lastname: Demasi
authors.forename: Alicia J
authors.initials: AJ
authors.lastname: Kowaltowski
mesh_terms: D000375:Aging / Q000502:physiology*; D031204:Caloric Restriction; D002478:Cells, Cultured; D004789:Enzyme Activation; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010101:Oxygen Consumption; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D050050:Protein Carbonylation; D011506:Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D025801:Ubiquitin / Q000378:metabolism; D044764:Ubiquitin-Activating Enzymes / Q000172:deficiency; D056811:Unfolded Protein Response
chemical_list: D011506:Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex; D044764:Ubiquitin-Activating Enzymes