Mitochondrial hyperpolarization: a checkpoint of T-cell life, death and autoimmunity
Mitochondrial hyperpolarization: a checkpoint of T-cell life, death and autoimmunity
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DOI：
10.1016/j.it.2004.05.001
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发表时间：
2004-07-01
影响因子：
16.8
通讯作者：
Banki, K
中科院分区：
文献类型：
--
作者：
Perl, A;Gergely, P;Banki, K
T 细胞的激活、增殖和细胞死亡途径的选择取决于活性氧中间体 (ROI) 的产生和 ATP 合成，而这些都受到线粒体跨膜电位 (Deltapsi(m)) 的严格调节。线粒体超极化 (MHP) 和 ATP 耗竭代表 T 细胞激活和凋亡的早期可逆步骤。相比之下，系统性红斑狼疮 (SLE) 患者的 T 细胞表现出持续的 MHP、细胞质碱化、ROI 产生增加和 ATP 耗尽，从而介导自发性增强和激活诱导的细胞凋亡减少，并使狼疮 T 细胞对坏死敏感。坏死但非凋亡的细胞裂解物激活树突状细胞，可能是狼疮患者干扰素α产生增加和炎症的原因。 MHP 被认为是 SLE 发病机制的关键机制，因此是药物干预的目标。
T-cell activation, proliferation and selection of the cell death pathway depend on the production of reactive oxygen intermediates (ROIs) and ATP synthesis, which are tightly regulated by the mitochondrial transmembrane potential (Deltapsi(m)). Mitochondrial hyperpolarization (MHP) and ATP depletion represent early and reversible steps in T-cell activation and apoptosis. By contrast, T cells of patients with systemic lupus erythematosus (SLE) exhibit persistent MHP, cytoplasmic alkalinization, increased ROI production and depleted ATP, which mediate enhanced spontaneous and diminished activation-induced apoptosis and sensitize lupus T cells to necrosis. Necrotic, but not apoptotic, cell lysates activate dendritic cells and might account for increased interferon alpha production and inflammation in lupus patients. MHP is proposed as a key mechanism of SLE pathogenesis and is therefore a target for pharmacological intervention.