Fig. 6.

Modulation of ER calcium levels by small molecules alters mutant protein-chaperone interaction and restores proteostasis. The activity of ER-resident chaperones are regulated by calcium. Increased ER calcium concentration is beneficial for those misfolded-prone proteins (such as those involved in different lysosomal storage diseases), which require chaperone-assisted folding (left panel). On the contrary, a reduction in ER calcium levels allows ΔF508CFTR to escape from chaperone-mediated proteasomal degradation (right panel). The question mark indicates that the original findings on thapsigargin and curcumin were not reproducible.