Using a high-throughput mitochondrial phenotyping platform to quantify multiple mitochondrial features among molecularly-defined immune cell subtypes, we quantify the natural variation in citrate synthase, mitochondrial DNA copy number (mtDNAcn), and respiratory chain enzymatic activities in human neutrophils, monocytes, B cells, and naïve and memory T lymphocyte subtypes. In mixed peripheral blood mononuclear cells (PBMCs) from the same individuals, we show to what extent mitochondrial measures are confounded by both cell type distributions and contaminating platelets. Cell subtype-specific measures among women and men spanning 4 decades of life indicate potential age- and sex-related differences, including an age-related elevation in mtDNAcn, which are masked or blunted in mixed PBMCs. Finally, a proof-of-concept, repeated-measures study in a single individual validates cell type differences and also reveals week-to-week changes in mitochondrial activities. Larger studies are required to validate and mechanistically extend these findings. These mitochondrial phenotyping data build upon established immunometabolic differences among leukocyte sub-populations, and provide foundational quantitative knowledge to develop interpretable blood-based assays of mitochondrial health.

中文翻译：

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纯化的人类免疫细胞亚型和细胞混合物中的线粒体表型

使用高通量线粒体表型平台量化分子定义的免疫细胞亚型中的多个线粒体特征，我们量化了柠檬酸合酶、线粒体 DNA 拷贝数 (mtDNAcn) 和呼吸链酶活性的自然变异，在人类中性粒细胞、单核细胞、B细胞，以及幼稚和记忆 T 淋巴细胞亚型。在来自同一个体的混合外周血单核细胞 (PBMC) 中，我们展示了线粒体测量在多大程度上受到细胞类型分布和污染血小板的混淆。跨越 4 年生命的女性和男性的细胞亚型特异性测量表明潜在的年龄和性别相关差异，包括与年龄相关的 mtDNAcn 升高，这在混合 PBMC 中被掩盖或减弱。最后，一个概念验证，单个个体的重复测量研究验证了细胞类型的差异，并揭示了线粒体活动的每周变化。需要更大规模的研究来验证和机械地扩展这些发现。这些线粒体表型数据建立在白细胞亚群之间已建立的免疫代谢差异的基础上，并为开发可解释的基于血液的线粒体健康测定提供了基础定量知识。