Macroautophagy and Chaperone-Mediated Autophagy in Heart Failure: The Known and the Unknown

Abstract

Cardiac diseases including hypertrophic and ischemic cardiomyopathies are increasingly being reported to accumulate misfolded proteins and damaged organelles. These findings have led to an increasing interest in protein degradation pathways, like autophagy, which are essential not only for normal protein turnover but also in the removal of misfolded and damaged proteins. Emerging evidence suggests a previously unprecedented role for autophagic processes in cardiac physiology and pathology. This review focuses on the major types of autophagic processes, the genes and protein complexes involved, and their regulation. It discusses the key similarities and differences between macroautophagy, chaperone-mediated autophagy, and selective mitophagy structures and functions. The genetic models available to study loss and gain of macroautophagy, mitophagy, and CMA are discussed. It defines the markers of autophagic processes, methods for measuring autophagic activities, and their interpretations. This review then summarizes the major studies of autophagy in the heart and their contribution to cardiac pathology. Some reports suggest macroautophagy imparts cardioprotection from heart failure pathology. Meanwhile, other studies find macroautophagy activation may be detrimental in cardiac pathology. An improved understanding of autophagic processes and their regulation may lead to a new genre of treatments for cardiac diseases.