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Protein quality control during aging involves recruitment of the macroautophagy pathway by BAG3
Author(s) -
Gamerdinger Martin,
Hajieva Parvana,
Kaya A Murat,
Wolfrum Uwe,
Hartl F Ulrich,
Behl Christian
Publication year - 2009
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2009.29
Subject(s) - biology , bag3 , autophagy , microbiology and biotechnology , genetics , apoptosis
The Hsc/Hsp70 co‐chaperones of the BAG (Bcl‐2‐associated athanogene) protein family are modulators of protein quality control. We examined the specific roles of BAG1 and BAG3 in protein degradation during the aging process. We show that BAG1 and BAG3 regulate proteasomal and macroautophagic pathways, respectively, for the degradation of polyubiquitinated proteins. Moreover, using models of cellular aging, we find that a switch from BAG1 to BAG3 determines that aged cells use more intensively the macroautophagic system for turnover of polyubiquitinated proteins. This increased macroautophagic flux is regulated by BAG3 in concert with the ubiquitin‐binding protein p62/SQSTM1. The BAG3/BAG1 ratio is also elevated in neurons during aging of the rodent brain, where, consistent with a higher macroautophagy activity, we find increased levels of the autophagosomal marker LC3‐II as well as a higher cathepsin activity. We conclude that the BAG3‐mediated recruitment of the macroautophagy pathway is an important adaptation of the protein quality control system to maintain protein homeostasis in the presence of an enhanced pro‐oxidant and aggregation‐prone milieu characteristic of aging.