Derlin Dfm1 employs a chaperone-like function to resolve misfolded membrane protein stress

Protein aggregates are a common feature of diseased and aged cells. Membrane
proteins comprise a quarter of the proteome, and yet, it is not well understood how
aggregation of membrane proteins is regulated and what effects these aggregates can
have on cellular health. We have determined in yeast that the derlin Dfm1 is has a
chaperone-like activity that influences misfolded membrane protein aggregation. We
establish that this function of Dfm1 does not require recruitment of the ATPase Cdc48
and it is distinct from Dfm1’s previously identified function in dislocating misfolded
membrane proteins to the cytosol for degradation. Additionally, we assess the cellular
impacts of misfolded membrane proteins in the absence of Dfm1 and determine that
misfolded membrane proteins are toxic to cells in the absence of Dfm1 and cause
disruptions to proteasomal and ubiquitin homeostasis.