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

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

Affiliations
  • 1Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, NY, USA. xl15@nyu.edu
  • 2Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
  • 3Perlmutter Cancer Institute, New York University Grossman School of Medicine, New York, NY, USA.
  • 4Department of Urology, New York University Grossman School of Medicine, New York, NY, USA.

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.

Keyword

Succinates; Microbiota; Inflammation; SUCNR1 protein; Periodontitis

MeSH Terms

Gastrointestinal Microbiome
Inflammation
Learning
Microbiota
Periodontitis
Succinates
Succinic Acid*
Succinates
Succinic Acid

Figure

  • Fig. 1 Expression levels of signals via the succinate receptor 1 (SUCNR1) mRNA in various tissues of mice. A 12-week-old C57BL/6J male mouse was euthanized before the organs were isolated and snap frozen with liquid nitrogen. The samples were stored at −80℃ until RNA extraction. An age matched C57BL/6J female mouse's ovary was collected and stored in the same way. Total RNA was isolated using TRI Reagent (Sigma-Aldrich), and purified using the RNeasy kit (Qiagen). Following TaqMan reverse transcription, polymerase chain reaction was performed in a BioRad 384-module using a SYBR Green (Applied Biosystems) method with primers for the indicated genes: β-actin forward primer: 5′-AGCCATGTACGTAGCCATCC-3′; β-actin reverse primer:5′-CTCTCAGCTGTGGTGGTGAA-3′. SUCNR1 forward primer: 5′-GACAGAAGCCGACAGCAGAAT-3′; SUCNR1 reverse primer: 5′-TAGACATTGCTGCTGTTCCAGTT-3′.


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