Confinement to Organelle-Associated Inclusion Structures Mediates Asymmetric Inheritance of Aggregated Protein in Budding Yeast

SummaryThe division of the S. cerevisiae budding yeast, which produces one mother cell and one daughter cell, is asymmetric with respect to aging. Remarkably, the asymmetry of yeast aging coincides with asymmetric inheritance of damaged and aggregated proteins by the mother cell. Here, we show that misfolded proteins are retained in the mother cell by being sequestered in juxtanuclear quality control compartment (JUNQ) and insoluble protein deposit (IPOD) inclusions, which are attached to organelles. Upon exposure to stress, misfolded proteins accumulate in stress foci that must be disaggregated by Hsp104 in order to be degraded or processed to JUNQ and IPOD. Cells that fail to deliver aggregates to an inclusion pass on aggregates to subsequent generations.

Graphical AbstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Misfolded proteins form stress foci, JUNQ inclusions, or IPOD inclusions ► JUNQs and IPODs are attached to organelles ► JUNQ and IPOD inclusions are asymmetrically inherited during cell division ► Hsp104 is required for disaggregation of stress foci