mTOR Signaling in Metabolic Stress Adaptation

Biomolecules. 2021 May 1;11(5):681. doi: 10.3390/biom11050681.

Abstract

The mechanistic target of rapamycin (mTOR) is a central regulator of cellular homeostasis that integrates environmental and nutrient signals to control cell growth and survival. Over the past two decades, extensive studies of mTOR have implicated the importance of this protein complex in regulating a broad range of metabolic functions, as well as its role in the progression of various human diseases. Recently, mTOR has emerged as a key signaling molecule in regulating animal entry into a hypometabolic state as a survival strategy in response to environmental stress. Here, we review current knowledge of the role that mTOR plays in contributing to natural hypometabolic states such as hibernation, estivation, hypoxia/anoxia tolerance, and dauer diapause. Studies across a diverse range of animal species reveal that mTOR exhibits unique regulatory patterns in an environmental stressor-dependent manner. We discuss how key signaling proteins within the mTOR signaling pathways are regulated in different animal models of stress, and describe how each of these regulations uniquely contribute to promoting animal survival in a hypometabolic state.

Keywords: Akt; TOR; anoxia; cell signaling; dauer; environmental stress; estivation; hibernation; hypoxia; metabolism; protein translation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptation, Physiological / physiology
  • Animals
  • Cell Cycle
  • Cell Proliferation
  • Diapause / physiology
  • Estivation / physiology
  • Hibernation / physiology
  • Humans
  • Mechanistic Target of Rapamycin Complex 1 / metabolism
  • Mechanistic Target of Rapamycin Complex 2 / metabolism
  • Signal Transduction / physiology
  • Stress, Physiological / physiology*
  • TOR Serine-Threonine Kinases / metabolism*
  • TOR Serine-Threonine Kinases / physiology*

Substances

  • Mechanistic Target of Rapamycin Complex 1
  • Mechanistic Target of Rapamycin Complex 2
  • TOR Serine-Threonine Kinases