Autophagy and the Ubiquitin-Proteasome System in Cardiac Dysfunction

The UPS degrades soluble misfolded proteins. Aberrant protein aggregation impairs proteasome proteolytic function and insufficient proteasome function in turn further accumulates misfolded proteins, thereby forming a vicious cycle. The inadequate or impaired UPS might activate the autophagy-lysosome pathway as a compensatory mechanism. The autophagy-lysosome pathway removes both soluble oligomers of misfolded proteins and protein aggregates. p62 and NBR1 recognize ubiquitinated proteins and mediate their autophagic degradation. HDAC6 binds to ubiquitinated proteins and facilitates their transportation along microtubules toward the microtubule organizing center (MTOC), where ubiquitinated proteins are organized into aggresomes. Moreover, the autophagic degradation of aggresomes is promoted by HDAC6. As co-chaperones, BAG1 and BAG3 regulate proteasomal and autophagic pathways, respectively.

Publication

Autophagy and the Ubiquitin-Proteasome System in Cardiac Dysfunction. () Qingwen Zheng, et al. Panminerva Med. ;52(1):9-25. Figure: F2. All organisms Mus musculus Homo sapiens Rattus norvegicus Sus scrofa Drosophila melanogaster Danio rerio Arabidopsis thaliana

Disease mentions