Sestrins: Darkhorse in the regulation of mitochondrial health and metabolism
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REVIEW
Sestrins: Darkhorse in the regulation of mitochondrial health and metabolism Ashish Kumar1 · Deepshikha Dhiman2 · Chandrima Shaha3 Received: 25 June 2020 / Accepted: 28 August 2020 © Springer Nature B.V. 2020
Abstract 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. Keywords Sestrin2 · Mitochondria · Metabolism · Health Abbreviations SESN2 Sestrin2 NRF2 Nuclear factor E2-related factor 2 AMPK AMP‐activated protein kinase mTOR Mammalian target of rapamycin ROS Reactive oxygen species RNS Reactive nitrogen species PRX1 Peroxiredoxin1 PRX2 Peroxiredoxin 2 PINK1 PTEN-induced kinase ATP Adenosine triphosphate Rag Rag GTPases ER Endoplasmic reticulum
* Ashish Kumar [email protected] 1
Department of Biotechnology, University of Helsinki, Helsinki, Finland
2
Dr. Yashwant Singh Parmar Govt. Medical College, Nahan, Himachal Pradesh, India
3
Cell Death and Differentiation Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India
Introduction A proximal symbiotic association between the aerobic bacteria and primordial eukaryotic cells was established billions of years ago, where the aerobic organisms turned out to be the energy house of the existing eukaryotic system [1–3]. These aerobic bacteria continued to exist in eukaryotic cells as their powerhouse that was termed as the “Mitochondrion”. In the course of evolution, mitochondria acquired the ability to sense and adapt against various cellular stresses [2]. Every type of stress signal which cells encounter converges to the mitochondria and to adapt against these stressors, mitochondria generates signals which coordinate to activate stress-responsive genes [4, 5]. Upon cellular damage, mitochondria functionality is disrupted resulting in the generation of a large amount of reactive oxygen species (ROS) [6, 7]. Many proteins are activated in response to stress sensed by the mitochondria. For example, mitochondrial damage and diverse cellular stresses induce transcript
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