Mitochondrial dysfunction in T cells of patients with systemic lupus erythematosus

Int Rev Immunol. May-Aug 2004;23(3-4):293-313. doi: 10.1080/08830180490452576.

Abstract

Activation, proliferation, or programmed cell death of T lymphocytes are dependent on controlled reactive oxygen intermediates (ROI) production and ATP synthesis in mitochondria. The mitochondrial transmembrane potential (Delta Psi(m)) also plays a decisive role in cell survival by controlling activity of redox-sensitive caspases. T lymphocytes of patients with systemic lupus erythematosus (SLE) exhibit mitochondrial hyperpolarization, increased ROI production, diminished intracellular glutathione levels, cytoplasmic alkalinization, and ATP depletion that mediate enhanced spontaneous and diminished activation-induced apoptosis and sensitize lupus T cells to necrosis. These redox and metabolic checkpoints represent novel targets for pharmacological intervention in SLE.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Apoptosis
  • Humans
  • Interleukin-10 / physiology
  • Interleukin-12 / physiology
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / metabolism
  • Lymphocyte Activation
  • Membrane Potentials
  • Mitochondria / immunology
  • Mitochondria / metabolism*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • Reactive Oxygen Species
  • Interleukin-10
  • Interleukin-12
  • Adenosine Triphosphate