Protein Degradation in Cardiac Health and Disease

Abstract

Protein quality control (PQC) is composed of co-translational and post-translational mechanisms that sense and minimize the level and toxicity of misfolded proteins in the cell. It is an essential part of proteostasis, involving intricate collaborations between chaperones and the targeted removal of misfolded proteins. The targeted degradation of misfolded proteins is performed primarily by the ubiquitin–proteasome system (UPS) although the autophagic-lysosomal pathway (ALP) also plays a supplemental role in the removal of misfolded proteins. Clinical evidence compellingly implicates a major role of UPS dysfunction in cardiac pathology. This chapter highlights the emerging evidence for a pivotal role of UPS dysfunction, especially proteasome functional insufficiency, in cardiac pathogenesis and discusses how the phosphoregulation of proteasome function may be potentially exploited to treat a large subset of heart diseases.