Sestrins: Darkhorse in the regulation of mitochondrial health and metabolism

Every disease is an outcome of one or more stress signals which get convened at the interface of the mitochondria. Mitochondria and metabolism are inextricably anchored to each other and a disruption in either can result in the generation of stressors, which can lead to detrimental health consequences. Stowing everything in one frame reflects that the proteins involved in the sensing of stressors are fundamental for the initiation of various pathologies and their detailed study is necessary for proper understanding of disease mechanisms. Sestrins, a class of evolutionarily conserved, stress inducible genes are activated by a wide range of stressors such as oxidative, genotoxic, and metabolic and play a role in cellular homeostasis. In addition, recent reports have highlighted their importance in governing the mitochondrial dynamics and metabolism. However, their spectrum of involvement in various pathologies has not been dissected out very well. This review will focus and discuss the role of Sestrins mainly Sestrin2 and associated nexus in the context of mitochondria, metabolism, and health.