Succinate: a metabolic signal in inflammation

Trends Cell Biol. 2014 May;24(5):313-20. doi: 10.1016/j.tcb.2013.11.008. Epub 2013 Dec 19.

Abstract

Succinate is an intermediate of the tricarboxylic acid (TCA) cycle, and plays a crucial role in adenosine triphosphate (ATP) generation in mitochondria. Recently, new roles for succinate outside metabolism have emerged. Succinate stabilizes the transcription factor hypoxia-inducible factor-1α (HIF-1α) in specific tumors and in activated macrophages, and stimulates dendritic cells via its receptor succinate receptor 1. Furthermore, succinate has been shown to post-translationally modify proteins. This expanding repertoire of functions for succinate suggests a broader role in cellular activation. We review the new roles of succinate and draw parallels to other metabolites such as NAD(+) and citrate whose roles have expanded beyond metabolism and into signaling.

Keywords: HIF-1α; SUCNR1; inflammation; metabolism; succinate; succinylation.

Publication types

  • Review

MeSH terms

  • Adaptive Immunity
  • Animals
  • Citric Acid Cycle
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / physiology
  • Immunity, Innate
  • Inflammation / metabolism*
  • Inflammation Mediators / metabolism
  • Protein Processing, Post-Translational
  • Receptors, G-Protein-Coupled / physiology
  • Signal Transduction
  • Succinic Acid / metabolism*

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Inflammation Mediators
  • Receptors, G-Protein-Coupled
  • Succinic Acid