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Emerging roles of molecular chaperones and co-chaperones in selective autophagy: focus on BAG proteins

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Abstract

Macroautophagy is a catabolic process by which the cell degrades cytoplasmic components through the lysosomal machinery. While initially acknowledged as a rather unspecific bulk degradation process, growing lines of evidence indicate the selectivity of macroautophagy pathways in the removal of misfolded or aggregated proteins. How such substrates are recognized and specifically targeted to the macroautophagy machinery has become a hotspot of investigation, and recent evidence suggests that here molecular chaperones and co-chaperones play a central role. One emerging pathway is mediated by the co-chaperone protein Bcl-2-associated athanogene 3 (BAG 3) which seems to utilize the specificity of molecular chaperones (heat-shock proteins) towards non-native proteins as basis for targeted macroautophagic degradation. In this short review, we focus on the molecular interplay between the macroautophagy system and molecular chaperones and highlight the relevance of the pathway mediated by BAG3 to aging and age-associated protein-misfolding diseases.

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Acknowledgments

The authors wish to thank Michael Plenikowski for artwork. This work was supported by grants from the Fritz-and-Hildegard-Berg-Foundation and the Peter-Beate-Heller-Foundation of the Stifterverband to C. Behl and by the Marie Curie International Reintegration Grant (PIRG-03-GA-2008-230908) and by the Prinses Beatrix Fonds/Dutch Huntington Association (WAR09-23) awarded to S. Carra.

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  1. Institute for Pathobiochemistry, University Medical Center, Johannes Gutenberg University, Duesbergweg 6, 55099, Mainz, Germany

    Martin Gamerdinger & Christian Behl

  2. Department of Cell Biology, Section for Radiation and Stress Cell Biology, University Medical Center Groningen, Groningen, The Netherlands

    Serena Carra

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  1. Martin Gamerdinger
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  2. Serena Carra
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  3. Christian Behl
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Correspondence to Christian Behl.

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Gamerdinger, M., Carra, S. & Behl, C. Emerging roles of molecular chaperones and co-chaperones in selective autophagy: focus on BAG proteins. J Mol Med 89, 1175–1182 (2011). https://doi.org/10.1007/s00109-011-0795-6

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