The role of the co-chaperone BAG3 in selective macroautophagy: implications for aging and disease
Maintenance of protein homeostasis, correct protein folding, refolding and clearance is of central importance for the function and survival of every cell. Here, the degradation of proteins is of particular importance, especially during aging and certain degenerative disorders when the protein load is increased. During cellular aging as well as under acute stress, there is a reciprocal change in expression of two members of the BAG (Bcl-2-associated athanogene) family, BAG1 and BAG3. While BAG1 serves an important function during the degradation of ubiquitinated proteins via the proteasome, BAG3 is the mediator of a novel macroautophagy pathway. This BAG3-mediated macroautophagy is based on the specificity of heat shock protein (HSP) 70 for misfolded proteins and also involves other protein partners, such as HSPB8, sequestosome-1/p62 (SQSTM1/p62) and the autophagosome protein LC3. BAG3 directly mediates the targeting and transport of degradation-prone substrates into aggresomes via the microtubule-motor dynein and also works independently of substrate ubiquitination.
KeywordsAmyotrophic Lateral Sclerosis Misfolded Protein Autophagy Pathway Cytosolic Component BAG3 Expression
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