SESTRINs: Emerging Dynamic Stress-Sensors in Metabolic and Environmental Health

Seung Hyun Ro, Julianne Fay, Cesar I. Cyuzuzo, Yura Jang, Naeun Lee, Hyun Seob Song, Edward N. Harris

Research output: Contribution to journalReview articlepeer-review

15 Scopus citations


Proper timely management of various external and internal stresses is critical for metabolic and redox homeostasis in mammals. In particular, dysregulation of mechanistic target of rapamycin complex (mTORC) triggered from metabolic stress and accumulation of reactive oxygen species (ROS) generated from environmental and genotoxic stress are well-known culprits leading to chronic metabolic disease conditions in humans. Sestrins are one of the metabolic and environmental stress-responsive groups of proteins, which solely have the ability to regulate both mTORC activity and ROS levels in cells, tissues and organs. While Sestrins are originally reported as one of several p53 target genes, recent studies have further delineated the roles of this group of stress-sensing proteins in the regulation of insulin sensitivity, glucose and fat metabolism, and redox-function in metabolic disease and aging. In this review, we discuss recent studies that investigated and manipulated Sestrins-mediated stress signaling pathways in metabolic and environmental health. Sestrins as an emerging dynamic group of stress-sensor proteins are drawing a spotlight as a preventive or therapeutic mechanism in both metabolic stress-associated pathologies and aging processes at the same time.

Original languageEnglish (US)
Article number603421
JournalFrontiers in Cell and Developmental Biology
StatePublished - Dec 3 2020


  • ROS
  • Sestrins
  • aging
  • cancer
  • environmental stress
  • mTORC
  • metabolic disease
  • obesity/inflammation

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology


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