Succinate: a metabolic signal in inflammation

E Mills, LAJ O'Neill - Trends in cell biology, 2014 - cell.com
Trends in cell biology, 2014cell.com
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 …
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.
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