[1][2][3][4] Autophagy (Greek: ‘self-eating’) was initially identified as a catabolic process for the unselective degradation of cellular content in lysosomes under starvation conditions.
[5][6] However, autophagy also comprises selective degradation pathways, which depend on ubiquitin conjugation to initiate sorting to lysosomes.
Chaperone-assisted selective autophagy is a vital part of the cellular protein quality control system.
It is essential for protein homeostasis (proteostasis) in neurons and in mechanically strained cells and tissues such as skeletal muscle, heart and lung.
[8] The aggresomes are stress-induced juxta-nuclear inclusion bodies that requires an intact microtubular network to colocalize misfolded proteins, molecular chaperones, and UPS components at the microtubule organizing center.
The activation of HSF1 is the primary mechanism by which heat shock, proteasome inhibition, oxidative stress, and other stressors increase BAG3 expression.
[4] Furthermore, the expression of the cochaperone BAG3 is upregulated in aged neuronal cells, which correlates with an increased necessity to dispose oxidatively damaged proteins through autophagy.
In mechanically strained cells and tissues, chaperone-assisted selective autophagy mediates the degradation of the actin-crosslinking protein filamin.