The life of [PSI]

The AAA+ disaggregase Hsp104 is essential for the maintenance and inheritance of nearly all known prions of the yeast Saccharomyces cerevisiae. Uniquely for [PSI+], the prion form of the Sup35 protein, there seem to be two activities, involving differing co-chaperones, by which Hsp104 affects the inheritance of [PSI+], the prion form of the Sup35 protein. Each pathway is also involved in protection against ageing, one through disaggregation of damaged proteins and the other through their retention in the mother cell during budding. Mutations in both Hsp104 and Sup35 affect prion inheritance by one or other of these pathways, as does manipulation of either Hsp104 enzyme activity or expression, in both vegetative (budding) divisions and in sporulation. Based on our recent finding (Ness et al. in Molec Microbiol 104:125–143, 2017) we suggest that the management of the heritable prion forms of Sup35 in [PSI+] cells in sporulation may be a marker for a role for Hsp104 in rejuvenation during sporulation.