Autophagy in the Heart

Abstract

The autophagic machinery is a well-conserved degradation system in eukaryotes from yeast to mammals. Autophagy has been thought of as a nonselective degradation process in which cytoplasmic proteins and organelles are degraded by fusion with lysosome. Recent studies have revealed selective forms of autophagy, such as mitochondria-specific autophagy, termed “mitophagy”. Research over the past decade has revealed that autophagy in cardiomyocytes plays a protective role, not only during hemodynamic stress but in homeostasis during aging. Hemodynamic stress and aging induce mitochondrial damage, leading to increased oxidative stress and decreased ATP production. Damaged mitochondria are generally degraded through mitophagy, which might be the main protective function of autophagy in the heart. Complete digestion of mitochondrial DNA through mitophagy is important to avoid inflammatory responses that can induce heart failure. A polyamine, spermidine, is reported to bring about an extension of lifespan and to protect the heart from age-related cardiac dysfunction, both of which are mediated through induction of autophagy. Therefore, appropriate induction of autophagy could be a novel therapeutic target for cardiovascular diseases, including heart failure. However, precise evaluation of autophagic activity in the human heart is difficult at this time, but exploitation of the novel technique of autophagy evaluation is expected for both drug discovery and clinical application.