Mitochondrial dysfunction in T cells of patients with systemic lupus erythematosus.
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.
Perl
Andras
A
Department of Medicine, State University of New York, Upstate Medical University, College of Medicine, Syracuse, New York 13210, USA. perla@upstate.edu
Gergely
Peter
P
Banki
Katalin
K
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D017209:Apoptosis; D006801:Humans; D016753:Interleukin-10 / Q000502:physiology; D018664:Interleukin-12 / Q000502:physiology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D008564:Membrane Potentials; D008928:Mitochondria / Q000276:immunology / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D017382:Reactive Oxygen Species; D016753:Interleukin-10; D018664:Interleukin-12; D000255:Adenosine Triphosphate