Succinate in innate immunity: linking metabolic reprogramming to immune modulation

Area of Science:

• Biochemistry
• Immunology
• Cellular Metabolism

Background:

• Succinate is a crucial metabolite in the tricarboxylic acid (TCA) cycle and connects it to the electron transport chain (ETC) for adenosine triphosphate (ATP) production.
• Emerging evidence highlights succinate's significant role in modulating immune cell functions.
• Succinate influences processes like reactive oxygen species (ROS) production, hypoxia-inducible factor-1α (HIF-1α) stabilization, protein succinylation, and cell-cell communication via succinate receptor 1 (SUCNR1).

Purpose of the Study:

• To provide a concise overview of succinate's regulatory functions in innate immune cells.
• To highlight the mechanisms through which succinate impacts innate immunity.
• To identify research gaps and potential therapeutic targets related to succinate in immunity.

Main Methods:

• Literature review focusing on the role of succinate in innate immunity.
• Analysis of mechanisms involving succinate, including ROS production, HIF-1α stabilization, protein succinylation, and SUCNR1 signaling.
• Examination of the dual role of succinate in inflammation (pro- or anti-inflammatory effects).

Main Results:

• Succinate exhibits context-dependent dual roles in inflammation, exerting either pro- or anti-inflammatory effects.
• Succinate influences key cellular processes relevant to immune responses in innate immune cells.
• The mechanisms of succinate's action in innate immunity are multifaceted and involve various signaling pathways.

Conclusions:

• Succinate is a critical regulator of innate immune cell function with significant implications for inflammatory processes.
• Understanding succinate's mechanisms in immunity offers potential for novel therapeutic strategies.
• Further research is needed to fully elucidate succinate's complex roles and therapeutic potential in innate immunity.