Apoptosis and mitochondrial dysfunction in lymphocytes of patients with systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is characterized by abnormal activation and cell death signaling within the immune system. Activation, proliferation, or death of cells of the immune system are dependent on controlled reactive oxygen intermediate (ROI) production and ATP synthesis in mitochondria. The mitochondrial transmembrane potential (Delta(Psi)m) reflects the energy stored in the electrochemical gradient across the inner mitochondrial membrane, which in turn is used by F0F1-ATPase to convert adenosine 5'-diphosphate to ATP during oxidative phosphorylation. Mitochondrial hyperpolarization and transient ATP depletion represent early and reversible steps in T-cell activation and apoptosis. By contrast, T lymphocytes of patients with SLE exhibit elevated Delta(Psi)m, that is, persistent mitochondrial hyperpolarization, cytoplasmic alkalinization, increased ROI production, as well as diminished levels of intracellular glutathione and ATP. Oxidative stress affects signaling through the T-cell receptor as well as the activity of redox-sensitive caspases. ATP depletion may be responsible for diminished activation-induced apoptosis and sensitize lupus T cells to necrosis. Mitochondrial dysfunction is identified as a key mechanism in the pathogenesis of SLE.
Perl
Andras
A
Department of Medicine, College of Medicine, Upstate Medical University, State University of New York, Syracuse, NY, USA.
Nagy
Gyorgy
G
Gergely
Peter
P
Puskas
Ferenc
F
Qian
Yueming
Y
Banki
Katalin
K
D000255:Adenosine Triphosphate / Q000032:analysis / Q000378:metabolism; D017209:Apoptosis; D015153:Blotting, Western; D020169:Caspases / Q000032:analysis / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005434:Flow Cytometry; D005978:Glutathione / Q000032:analysis / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D008213:Lymphocyte Activation; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D017382:Reactive Oxygen Species / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*
D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D020169:Caspases; D005978:Glutathione