The tricarboxylic acid cycle at the crossroad between cancer and immunity

Alessandra Scagliola, Francesco Mainini, Simone Cardaci

Research output: Contribution to journalReview articlepeer-review

Abstract

Significance: The tricarboxylic acid (TCA) cycle is a housekeeping metabolic pathway essential for generation of energy and biosynthetic intermediates. Alterations of the TCA cycle play a pivotal role in oncogenesis and inflammation. As such, some metabolic vulnerabilities, imposed by TCA cycle dysfunction in cancer, have been identified. Similarly, the TCA cycle appeared as an actionable pathway in immunopathologies. Recent Advances: Metabolic changes accompanying cell transformation have been usually considered as adaptive mechanisms to malignant transformation. The identification of oncogenic mutations in some TCA cycle enzymes changed this view, indicating altered mitochondrial metabolism as an instrumental mechanism for cancer initiation. Similarly, the observation that TCA cycle-derived metabolites have multiple signaling roles in immune cells supports the idea of this pathway as a metabolic rheostat of immune responses. Critical Issues: This review summarizes the crucial role of the TCA cycle in pathophysiology describing the post-translational and epigenetic impact of oncometabolites accumulation in cancer and immune cells. Future Directions: Additional studies will be necessary to further explore the role of oncometabolites in paracrine signaling and to identify genuine metabolic and nutritional liabilities imposed by TCA cycle dysfunction in cancer, hardly to be escaped by resistance mechanisms.

Original languageEnglish
Pages (from-to)834-852
Number of pages19
JournalAntioxidants and Redox Signaling
Volume32
Issue number12
DOIs
Publication statusPublished - Apr 20 2020

Keywords

  • cancer
  • inflammation
  • metabolic vulnerabilities
  • metabolism
  • oncometabolites

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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