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Succinate: a metabolic signal in inflammation
Evanna Mills1, Luke A J O'Neill1
1School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
Trends in Cell Biology
|December 24, 2013
Summary
Succinate, a key metabolic intermediate, also acts as a signaling molecule. It stabilizes hypoxia-inducible factor-1α (HIF-1α) and activates immune cells, revealing broader roles beyond energy production.
Area of Science:
- Biochemistry
- Cellular Biology
- Immunology
Background:
- Succinate is a crucial intermediate in the tricarboxylic acid (TCA) cycle, essential for adenosine triphosphate (ATP) generation in mitochondria.
- Emerging evidence indicates significant roles for succinate beyond its metabolic functions.
Purpose of the Study:
- To review the non-metabolic functions of succinate.
- To highlight succinate's emerging roles in cellular activation and signaling pathways.
- To draw parallels with other metabolites like NAD(+) and citrate that have expanded roles.
Main Methods:
- Literature review of recent studies on succinate's functions.
- Analysis of succinate's involvement in protein stabilization and immune cell stimulation.
- Comparative analysis with other signaling metabolites.
Main Results:
- Succinate stabilizes the transcription factor hypoxia-inducible factor-1α (HIF-1α) in tumors and macrophages.
- Succinate stimulates dendritic cells through the succinate receptor 1.
- Succinate participates in post-translational protein modification.
Conclusions:
- Succinate possesses diverse signaling functions, extending beyond its established metabolic role.
- These non-metabolic functions suggest a broader involvement in cellular activation and immune responses.
- Succinate represents a key metabolite with dual metabolic and signaling capabilities.
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