The roles of the inhibitory autophagy regulator Rubicon in the heart: A new therapeutic target to prevent cardiac cell death.

Autophagy contributes to the maintenance of cardiac homeostasis. The level of autophagy is dynamically altered in heart disease. Although autophagy is a promising therapeutic target, only a few selective autophagy activator candidates have been reported thus far. Rubicon is one of the few endogenous negative regulators of autophagy and a potential target for autophagy-inducing therapeutics. Rubicon was initially identified as a component of the Class III PI3K complex, and it has multiple functions, not only in canonical autophagy but also in endosomal trafficking and inflammatory responses. This review summarizes the molecular action of Rubicon in canonical and noncanonical autophagy. We discuss the roles of Rubicon in cardiac stress and the therapeutic potential of Rubicon in cardiac diseases through its modulation of autophagy. A protein known as Rubicon, which inhibits the routine degradation of cell components in a process called autophagy, has been identified as a possible target for drugs to prevent the death of heart muscle cells. Autophagy is required for healthy cell maintenance and its failure has been linked to heart disease, cancer, metabolic disorder and aging. Jihoon Nah and colleagues at Rutgers New Jersey Medical School, Newark, USA, review the role of Rubicon in health and disease. The authors discuss how Rubicon suppresses autophagy in ways that could promote cell death and disease, focusing especially on the heart. They also identify significant areas where understanding of Rubicon’s regulatory effects is lacking. Some molecules that interfere with Rubicon’s activity have already been identified. Further research could yield new treatments for heart disease and other conditions.