4.6 Review

The nexus between redox state and intermediary metabolism

Journal

FEBS JOURNAL
Volume 289, Issue 18, Pages 5440-5462

Publisher

WILEY
DOI: 10.1111/febs.16191

Keywords

anabolism; intermediary metabolism; reactive oxygen species; redox; warburg effect

Funding

  1. British Heart Foundation [CH/1999001/11735, RE/18/2/34213, RM/17/3/33381]
  2. National Institute for Health Research Biomedical Research Centre at Guy's & St Thomas' NHS Foundation Trust [IS-BRC-1215-20006]
  3. King's College London [IS-BRC-1215-20006]
  4. Fondation Leducq Transatlantic Network of Excellence [17CVD04]

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Reactive oxygen species (ROS) serve as signaling molecules that regulate physiological and pathophysiological processes by influencing the redox homeostasis and metabolic pathways within cells. Understanding the interactions between ROS signaling, metabolic adaptation, and redox balance is crucial for developing novel therapeutic strategies to treat various diseases in different tissues.
Reactive oxygen species (ROS) are not just a by-product of cellular metabolic processes but act as signalling molecules that regulate both physiological and pathophysiological processes. A close connection exists in cells between redox homeostasis and cellular metabolism. In this review, we describe how intracellular redox state and glycolytic intermediary metabolism are closely coupled. On the one hand, ROS signalling can control glycolytic intermediary metabolism by direct regulation of the activity of key metabolic enzymes and indirect regulation via redox-sensitive transcription factors. On the other hand, metabolic adaptation and reprogramming in response to physiological or pathological stimuli regulate intracellular redox balance, through mechanisms such as the generation of reducing equivalents. We also discuss the impact of these intermediary metabolism-redox circuits in physiological and disease settings across different tissues. A better understanding of the mechanisms regulating these intermediary metabolism-redox circuits will be crucial to the development of novel therapeutic strategies.

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