Perl Andras, Hanczko Robert, Doherty Edward
Department of Medicine, State University of New York, Upstate Medical University, College of Medicine, Syracuse, NY, USA.
Methods Mol Biol. 2012;900:61-89. doi: 10.1007/978-1-60761-720-4_4.
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 is dependent on controlled reactive oxygen intermediates (ROI) production and ATP synthesis in mitochondria. The mitochondrial transmembrane potential (∆ψ (m)) reflects the energy stored in the electrochemical gradient across the inner mitochondrial membrane which, in turn, is used by F(0)F(1)-ATPase to convert ADP to ATP during oxidative phosphorylation. Mitochondrial hyperpolarization (MHP) 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 ∆ψ (m), i.e., persistent mitochondrial hyperpolarization (MHP), cytoplasmic alkalinization, increased ROI production, as well as diminished levels of intracellular glutathione and ATP. Increased production of nitric oxide has been identified as a cause of MHP and increased mitochondrial biogenesis. Oxidative stress affects signaling through the T cell receptor as well as activity of redox--sensitive caspases. ATP depletion causes diminished activation-induced apoptosis and sensitizes lupus T cells to necrosis. Activation of the mammalian target of rapamycin (mTOR) has recently emerged as a key sensor of MHP and mediator of enhanced Ca(2+) flux in lupus T cells.
系统性红斑狼疮（SLE）的特征是免疫系统内异常的激活和细胞死亡信号传导。免疫系统细胞的激活、增殖或死亡取决于线粒体中受控的活性氧中间体（ROI）产生和ATP合成。线粒体跨膜电位（∆ψ (m)）反映了跨线粒体内膜电化学梯度中储存的能量，而该能量又被F(0)F(1)-ATP酶用于在氧化磷酸化过程中将ADP转化为ATP。线粒体超极化（MHP）和短暂的ATP消耗代表T细胞激活和凋亡的早期且可逆步骤。相比之下，SLE患者的T淋巴细胞表现出∆ψ (m)升高，即持续性线粒体超极化（MHP）、细胞质碱化、ROI产生增加，以及细胞内谷胱甘肽和ATP水平降低。一氧化氮产生增加已被确定为MHP和线粒体生物发生增加的原因。氧化应激影响通过T细胞受体的信号传导以及氧化还原敏感半胱天冬酶的活性。ATP消耗导致激活诱导的凋亡减少，并使狼疮T细胞对坏死敏感。哺乳动物雷帕霉素靶蛋白（mTOR）的激活最近已成为狼疮T细胞中MHP的关键传感器和增强Ca(2+)通量的介质。
