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

We aimed to provide a comprehensive systematic overview of the molecular mechanisms of each tricarboxylic acid cycle cycle intermediate that may play key roles in regulating cellular immunity in cell stress and discuss its implication for immune activation and suppression

Inseok Choi; Hyewon Son; Jea-Hyun Baek

2021

Scholarcy highlights

  • The tricarboxylic acid cycle is a series of chemical reactions used in aerobic organisms to generate energy via the oxidation of acetyl-coenzyme A derived from carbohydrates, fatty acids and proteins
  • The TCA cycle occurs exclusively in the matrix of the mitochondria, which are surrounded by two lipid bilayers and impermeable to polar solutes
  • Of note, increasing evidence suggests that the TCA cycle intermediates play crucial roles in regulating cellular immunity
  • The mitochondrial membrane may be disrupted and release the TCA cycle intermediates into the cytosol, thereby impacting the cellular immunity
  • This review has provided insights into the immunological roles of TCA cycle intermediates that may leak from dysfunctioning mitochondria with
  • Activation of immune cells ates such as succinate, citrate, fumarate, and itaconate are thereby important regulators leads to the remodeling of the TCA cycle via a process called the “immunologic Warburg ofeffect”
  • Studies shown citrate and succinate pro-inflammatory properties, whereas itaconate,activation, α-ketoglutarate, and fumarate arethey linkedbalance immune lites are upregulated during immune indicating that more with immunosuppressive

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