Tricarboxylic Acid (TCA) Cycle Intermediates: Regulators of Immune Responses

The tricarboxylic acid cycle (TCA) is a series of chemical reactions used in aerobic organisms to generate energy via the oxidation of acetylcoenzyme A (CoA) derived from carbohydrates, fatty acids and proteins. In the eukaryotic system, the TCA cycle occurs completely in mitochondria, while the intermediates of the TCA cycle are retained inside mitochondria due to their polarity and hydrophilicity. Under cell stress conditions, mitochondria can become disrupted and release their contents, which act as danger signals in the cytosol. Of note, the TCA cycle intermediates may also leak from dysfunctioning mitochondria and regulate cellular processes. Increasing evidence shows that the metabolites of the TCA cycle are substantially involved in the regulation of immune responses. In this review, we aimed to provide a comprehensive systematic overview of the molecular mechanisms of each TCA cycle intermediate that may play key roles in regulating cellular immunity in cell stress and discuss its implication for immune activation and suppression.

Automated summary

The TCA cycle is a series of chemical reactions that occur in the mitochondria of aerobic organisms to generate energy from acetyl-CoA. The intermediates of the TCA cycle may leak from dysfunctional mitochondria and regulate immune responses under cell stress conditions. Increasing evidence suggests that the metabolites of the TCA cycle play important roles in the regulation of immune activation and suppression.