title: Autophagy and mitophagy in the myocardium: therapeutic potential and concerns.
abstract: The autophagic-lysosomal degradation pathway is critical for cardiac homeostasis, and defects in this pathway are associated with development of cardiomyopathy. Autophagy is responsible for the normal turnover of organelles and long-lived proteins. Autophagy is also rapidly up-regulated in response to stress, where it rapidly clears dysfunctional organelles and cytotoxic protein aggregates in the cell. Autophagy is also important in clearing dysfunctional mitochondria before they can cause harm to the cell. This quality control mechanism is particularly important in cardiac myocytes, which contain a very high volume of mitochondria. The degradation of proteins and organelles also generates free fatty acids and amino acids, which help maintain energy levels in myocytes during stress conditions. Increases in autophagy have been observed in various cardiovascular diseases, but a major question that remains to be answered is whether enhanced autophagy is an adaptive or maladaptive response to stress. This review discusses the regulation and role of autophagy in the myocardium under baseline conditions and in various aetiologies of heart disease. It also discusses whether this pathway represents a new therapeutic target to treat or prevent cardiovascular disease and the concerns associated with modulating autophagy.
authors.affiliation: Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla, CA, USA.
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Jimenez
authors.forename: Dieter A
authors.initials: DA
authors.lastname: Kubli
authors.forename: Åsa B
authors.initials: ÅB
authors.lastname: Gustafsson
mesh_terms: D018943:Anthracyclines / Q000009:adverse effects; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D006331:Heart Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D006706:Homeostasis; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology; D063306:Mitophagy / Q000502:physiology*; D008954:Models, Biological; D058990:Molecular Targeted Therapy / Q000379:methods*; D032383:Myocytes, Cardiac / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000502:physiology
chemical_list: D018943:Anthracyclines; C090121:BNIP3 protein, human; C116838:BNIP3L protein, human; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins
keywords: BNIP3; Parkin; autophagy; heart; mitochondria; mitophagy