Neuroprotective and other functional proteins of mitochondria were quantified in extracts of plasma neural-derived exosomes from ten first-episode psychosis (FP) patients and ten matched psychiatrically normal controls (ctls). Astrocyte-derived extracellular vesicles (ADEVs) and neuron-derived extracellular vesicles (NDEVs) were immunoabsorbed separately from physically precipitated plasma total EVs. Extracted mitochondrial ATP synthase was specifically immunofixed to plastic wells for quantification of catalytic activity based on conversion of NADH to NAD+ . Other extracted mitochondrial functional proteins were quantified by ELISAs. All protein levels were normalized with EV content of the CD81 exosome marker. FP patient ADEV level but not NDEV level of mitochondrial ATP synthase activity was significantly lower than that of ctls. FP patient ADEV and NDEV levels of the functionally critical mitochondrial proteins mitofusin 2 and cyclophilin D, but not of transcription factor A of mitochondria, and of the mitochondrial short open-reading frame neuroprotective and metabolic regulatory peptides humanin and MOTS-c were significantly lower than those of ctls. In contrast, FP patient NDEV, but not ADEV, level of the mitochondrial-tethering protein syntaphilin, but not of myosin VI, was significantly higher than that of ctls. The distinctively different neural levels of some mitochondrial proteins in FP patients than ctls now should be correlated with diverse clinical characteristics. Drugs that increase depressed levels of proteins and mimetics of deficient short open-reading frame peptides may be of therapeutic value in early phases of schizophrenia.

中文翻译：

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神经细胞源性血浆外泌体蛋白异常表明精神病首次发作时线粒体受损


对来自 10 名首发精神病 (FP) 患者和 10 名匹配的精神正常对照 (ctls) 的血浆神经源性外泌体提取物中的线粒体神经保护蛋白和其他功能蛋白进行了定量。星形胶质细胞来源的细胞外囊泡 (ADEV) 和神经元来源的细胞外囊泡 (NDEV) 与物理沉淀的血浆总 EV 分开进行免疫吸收。将提取的线粒体 ATP 合酶特异性免疫固定到塑料孔中，以根据 NADH 转化为 NAD+ 的催化活性进行定量。其他提取的线粒体功能蛋白通过 ELISA 进行定量。所有蛋白质水平均以 CD81 外泌体标记物的 EV 含量标准化。 FP患者的线粒体ATP合成酶活性的ADEV水平而非NDEV水平显着低于ctls。 FP 患者功能关键线粒体蛋白线粒体融合蛋白 2 和亲环蛋白 D 的 ADEV 和 NDEV 水平显着低于线粒体转录因子 A，以及线粒体短开放阅读框神经保护和代谢调节肽人素和 MOTS-c 的水平。 ctls 的那些。相比之下，FP患者NDEV（而非ADEV）、线粒体束缚蛋白亲合蛋白（而非肌球蛋白VI）的水平显着高于ctls。 FP 患者中一些线粒体蛋白的神经水平与现在的 ctl 明显不同，这应该与不同的临床特征相关。增加蛋白质和短开放阅读框肽缺陷模拟物水平的药物可能在精神分裂症的早期阶段具有治疗价值。