Biochemical basis and metabolic interplay of redox regulation

Redox Biol. 2019 Sep:26:101284. doi: 10.1016/j.redox.2019.101284. Epub 2019 Aug 2.

Abstract

Accumulated evidence strongly indicates that oxidative stress, characterized by an imbalance between reactive oxygen species (ROS) production and antioxidants in favor of oxidants, plays an important role in disease pathogenesis. However, ROS can act as signaling molecules and fulfill essential physiological functions at basal levels. Each ROS would be different in the extent to stimulate and contribute to different pathophysiological effects. Importantly, multiple ROS generators can be activated either concomitantly or sequentially by relevant signaling molecules for redox biological functions. Here, we summarized the current knowledge related to chemical and biochemical features of primary ROS species and corresponding antioxidants. Metabolic pathways of five major ROS generators and five ROS clearance systems were described, including their ROS products, specific ROS enriched tissue, cell and organelle, and relevant functional implications. We provided an overview of ROS generation and induction at different levels of metabolism. We classified 11 ROS species into three types based on their reactivity and target selectivity and presented ROS homeostasis and functional implications in pathological and physiological status. This article intensively reviewed and refined biochemical basis, metabolic signaling and regulation, functional insights, and provided guidance for the identification of novel therapeutic targets.

Keywords: Antioxidants; ROS generators; Redox regulation and homeostasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Energy Metabolism* / genetics
  • Homeostasis
  • Humans
  • Mice
  • Mice, Knockout
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Oxidation-Reduction*
  • Oxidative Stress / genetics
  • Phenotype
  • Reactive Oxygen Species / metabolism

Substances

  • Antioxidants
  • Reactive Oxygen Species