Chapter 27 - Protein Quality Control in Cardiomyocytes

Abstract

Protein quality control (PQC) plays an indispensable role in maintaining protein homeostasis in cardiomyocytes. PQC is a fundamental cellular process, whose role it is to sense and repair misfolded/unfolded proteins and, if the repair fails, degrade the terminally misfolded polypeptides through an intricate collaboration between molecular chaperones and targeted proteolysis. Proteolysis of damaged proteins is performed primarily by the ubiquitin–proteasome system (UPS). The development of a range of heart diseases, including bona fide cardiac proteinopathies and various forms of cardiac dysfunction, have been linked to inadequacies in the PQC system. PQC inadequacy due to chaperone insufficiency and/or proteasome functional insufficiency has been shown to contribute to the progression of these diseases to chronic heart failure (CHF). Therefore, measures taken to enhance PQC in cardiomyocytes are expected to slow down the progression of a large subset of heart diseases and possibly prevent the escalation of these conditions to CHF.