Multifaceted Actions of Succinate as a Signaling Transmitter Vary with Its Cellular Locations

Endocrinol Metab (Seoul). 2020 Mar;35(1):36-43. doi: 10.3803/EnM.2020.35.1.36.

Abstract

Since the identification of succinate's receptor in 2004, studies supporting the involvement of succinate signaling through its receptor in various diseases have accumulated and most of these investigations have highlighted succinate's pro-inflammatory role. Taken with the fact that succinate is an intermediate metabolite in the center of mitochondrial activity, and considering its potential regulation of protein succinylation through succinyl-coenzyme A, a review on the overall multifaceted actions of succinate to discuss whether and how these actions relate to the cellular locations of succinate is much warranted. Mechanistically, it is important to consider the sources of succinate, which include somatic cellular released succinate and those produced by the microbiome, especially the gut microbiota, which is an equivalent, if not greater contributor of succinate levels in the body. Continue learning the critical roles of succinate signaling, known and unknown, in many pathophysiological conditions is important. Furthermore, studies to delineate the regulation of succinate levels and to determine how succinate elicits various types of signaling in a temporal and spatial manner are also required.

Keywords: Inflammation; Microbiota; Periodontitis; SUCNR1 protein; Succinates.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Inflammation / metabolism
  • Inflammation / pathology*
  • Inflammation Mediators / metabolism*
  • Metabolic Diseases / metabolism
  • Metabolic Diseases / pathology*
  • Protein Processing, Post-Translational
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction
  • Succinates / metabolism*

Substances

  • Inflammation Mediators
  • Receptors, G-Protein-Coupled
  • Succinates