The unfolded protein response maintains protein homeostasis in the endoplasmic reticulum (ER), where the majority of transmembrane and secretory proteins are modified, folded and assembled.
As subcellular compartments, organelles provide optimized conditions for distinct biochemical reactions. Explained by their endosymbiotic origin, mitochondria and chloroplasts retain their own unique genomes.
Protein-folding stress in the ER activates the endonuclease domain of the stress sensor Ire1, triggering two distinct responses: non-conventional mRNA splicing and regulated Ire1-dependent decay (RIDD) of mRNAs at the ER surface.
Cells maintain their proteins in a functional and balanced state by regulating protein synthesis, folding, trafficking and degradation.
One family of proteins that senses conditions in the ER and increases the organelle’s folding capacity is comprised of a family of membrane-bound transcription factors, named after the founding member ATF6 (activating transcription factor).