Environmental stress and protein-based inheritance

Self-perpetuating protein aggregates (amyloids) and their transmissible variety (prions) are associated with some human diseases. Yeast self-perpetuating protein isoforms (yeast prions) control heritable traits. Metastable prions and non-transmissible aggregates (mnemons) control cellular memory of environmental or physiological changes. Stress-inducible chaperones control prion propagation. De novo prion formation is counteracted by the ribosome-associated chaperone complex. Environmental stresses and proteotoxic agents lead to massive accumulation of damaged aggregated proteins. Toxic effects of stress-induced protein aggregation are counteracted by the disaggregating chaperone machinery and by the spatial control apparatus, assuring asymmetric accumulation of aggregated proteins in the mother cell after cell division. Prions hijack the chaperone machinery for the purpose of their own propagation and escape the spatial control, that enables them to be inherited by daughter cells. Our data show that while environmental stress promotes formation of some prions, it also counteracts prion propagation via influencing the proteostasis networks and activating the spatial control machinery. Depletion of the ribosome-associated chaperone Hsp70-Ssb stabilizes some prions during stress and promotes both de novo formation and propagation of the protein-based determinants of cell memory. Defect of the spatial control machinery in the cells lacking the protein deacetylase Sir2 also results in prion stabilization under stress conditions. Cell aging impacts prion formation and propagation in a manner similar to environmental stress. Overall, the stress- and aging-related protein quality control machineries of the cell plays an important role in the processes of prion formation and propagation in yeast. An impact of environmental and aging-related stress on heritable protein aggregation, detected in yeast, could be applicable to human amyloid diseases. (Supported by NSF, RSF and RFBR.)