FAIM opposes stress-induced loss of viability and blocks the formation of protein aggregates

A number of proteinopathies are associated with accumulation of misfolded proteins, which form pathological insoluble deposits. It is hypothesized that molecules capable of blocking formation of such protein aggregates might avert disease onset or delay disease progression. Here we report that Fas Apoptosis Inhibitory Molecule (FAIM) counteracts stress-induced loss of viability. We found that levels of ubiquitinated protein aggregates produced by cellular stress are much greater in FAIM-deficient cells and tissues. Moreover, in an in vitro cell-free system, FAIM specifically and directly prevents pathological protein aggregates without participation by other cellular elements, in particular the proteasomal and autophagic systems. Although this activity is similar to the function of heat shock proteins (HSP s ), FAIM, which is highly conserved throughout evolution, bears no homology to any other protein, including HSP s . These results identify a new actor that protects cells against stress-induced loss of viability by preventing protein aggregates.