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Apoptosis and Mitochondrial Dysfunction in Lymphocytes of Patients With Systemic Lupus Erythematosus

  • Protocol
Autoimmunity

Part of the book series: Methods in Molecular Medicine™ ((MIMM,volume 102))

Summary

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 (ΔΨm) 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 ΔΨm, 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.

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Authors and Affiliations

  1. Division of Rheumatology, Departments of Medicine and of Microbiology and Immunology, College of Medicine, Upstate Medical University, State University of New York, Syracuse, NY

    Andras Perl

  2. Division of Rheumatology, Department of Medicine, College of Medicine, Syracuse, NY

    Gyorgy Nagy, Ferenc Puskas & Yueming Qian

  3. Division of Rheumatology, Department of Medicine, State University of New York, Upstate Medical University College of Medicine, Syracuse, NY

    Peter Gergely

  4. Department of Pathology, State University of New York, Upstate Medical University College of Medicine, Syracuse, NY

    Katalin Banki

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  3. Peter Gergely
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  4. Ferenc Puskas
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  5. Yueming Qian
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  6. Katalin Banki
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Editor information

Editors and Affiliations

  1. Departments of Medicine, Microbiology, and Immunology, State University of New York, Upstate Medical University, College of Medicine, Syracuse, NY

    Andras Perl MD, PhD

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© 2004 Humana Press Inc., Totowa, NJ

About this protocol

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Perl, A., Nagy, G., Gergely, P., Puskas, F., Qian, Y., Banki, K. (2004). Apoptosis and Mitochondrial Dysfunction in Lymphocytes of Patients With Systemic Lupus Erythematosus. In: Perl, A. (eds) Autoimmunity. Methods in Molecular Medicine™, vol 102. Humana Press. https://doi.org/10.1385/1-59259-805-6:087

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  • DOI: https://doi.org/10.1385/1-59259-805-6:087

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-231-5

  • Online ISBN: 978-1-59259-805-2

  • eBook Packages: Springer Protocols

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