Figure 3.

The role of co-chaperones in cardiac protein quality control. Heat shock proteins, including HSP70, coordinate with co-chaperones to maintain proteostasis in the heart. Impairment of cardiac protein quality control can lead to distinct forms of heart disease, including left ventricular hypertrophy, dilated cardiomyopathy, and myocardial infarction. Loss-of-function in the co-chaperone proteins CryAB, BAG3, and CHIP alters chaperone function and the ability to maintain proteostasis, leading to heart disease. Missense mutations in CryAB and BAG3 cause heritable forms of cardiomyopathies (purple and orange). Loss of CryAB or BAG3 function can lead to left ventricular hypertrophy or increased susceptibility to infarction, respectively. Finally, the ability of CHIP to ubiquitinate regulatory proteins in cardiomyocytes (green) is necessary to prevent cardiac hypertrophy and cell death in response to myocardial infarction.