Succinyl-CoA Ligase Deficiency in Pro-inflammatory and Tissue-Invasive T Cells

Bowen Wu, Jingtao Qiu, Tuantuan V. Zhao, Yanan Wang, Toshihisa Maeda, Isabel N. Goronzy, Mitsuhiro Akiyama, Shozo Ohtsuki, Ke Jin, Lu Tian, Jörg J. Goronzy, Cornelia M. Weyand

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Autoimmune T cells in rheumatoid arthritis (RA) have a defect in mitochondrial oxygen consumption and ATP production. Here, we identified suppression of the GDP-forming β subunit of succinate-CoA ligase (SUCLG2) as an underlying abnormality. SUCLG2-deficient T cells reverted the tricarboxylic acid (TCA) cycle from the oxidative to the reductive direction, accumulated α-ketoglutarate, citrate, and acetyl-CoA (AcCoA), and differentiated into pro-inflammatory effector cells. In AcCoAhi RA T cells, tubulin acetylation stabilized the microtubule cytoskeleton and positioned mitochondria in a perinuclear location, resulting in cellular polarization, uropod formation, T cell migration, and tissue invasion. In the tissue, SUCLG2-deficient T cells functioned as cytokine-producing effector cells and were hyperinflammatory, a defect correctable by replenishing the enzyme. Preventing T cell tubulin acetylation by tubulin acetyltransferase knockdown was sufficient to inhibit synovitis. These data link mitochondrial failure and AcCoA oversupply to autoimmune tissue inflammation.

Original languageEnglish (US)
Pages (from-to)967-980.e5
JournalCell Metabolism
Issue number6
StatePublished - Dec 1 2020


  • T cell
  • acetyl-CoA
  • acetylation
  • alph-ketoglutarate
  • autoimmunity
  • citrate
  • microtubule
  • mitochondria
  • tissue invasion
  • uropod

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology


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