Misfolded proteins impose a dosage-dependent fitness cost and trigger a cytosolic unfolded protein response in yeast.

ABSTRACT: Evolving lineages face a constant intracellular threat: most new coding sequence mutations destabilize the folding of the encoded protein. Misfolded proteins form insoluble aggregates and are hypothesized to be intrinsically cytotoxic. Here, we experimentally isolate a fitness cost caused by toxicity of misfolded proteins. We exclude other costs of protein misfolding, such as loss of functional protein or attenuation of growth-limiting protein synthesis resources, by comparing growth rates of budding yeast expressing folded or misfolded variants of a gratuitous protein, YFP, at equal levels. We quantify a fitness cost that increases with misfolded protein abundance, up to as much as a 3.2% growth rate reduction when misfolded YFP represents less than 0.1% of total cellular protein. Compara

SUBMITTER: Geiler-Samerotte KA 

PROVIDER: S-EPMC3021021 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature