Succinate: a metabolic signal in inflammation.
By E. Mills, Luke A. O'Neill. Trends in Cell Biology, 2014
657 citations recorded by the source corpus.
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.
Subfields: Biochemistry, Cancer Research, Immunology
View Paper: https://www.semanticscholar.org/paper/2206bd3797e06f65c8cc5d2edc2dda9f1caf8760
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Citations in the corpus
- Metabolomics for Investigating Physiological and Pathophysiological Processes. (2019, background): “HIF-1 stimulates the production of growth factors, such as transforming growth factor- (TGF- ), insulin-like growth factor 2, and growth factor receptors, such as the epidermal growth factor receptor (EGFR), resulting in continuous proliferative signaling (146).”
- Mitochondria in the regulation of innate and adaptive immunity (2015, neutral): “Succinate dehydrogenase is the only TCA enzyme that also functions as an electron carrier in the electron transport chain, which might position it to also modulate ROS signaling (Mills and O’Neill, 2014).”
- Reactive oxygen species and mitochondria: A nexus of cellular homeostasis (2015, background): “Mitochondria and potentially mitochondrial ROS are also components of pathways regulating apoptosis [8], stem cell differentiation [9], autophagy [10], and cellular [11,12] and tissue-level [13] inflammation.”