Human mitochondrial diseases are a group of heterogeneous diseases caused by defects in oxidative phosphorylation, due to mutations in mitochondrial (mtDNA) or nuclear DNA. The diagnosis of mitochondrial disease is challenging since mutations in multiple genes can affect mitochondrial function, there is considerable clinical variability and a poor correlation between genotype and phenotype. Herein we assessed mitochondrial function in peripheral blood mononuclear cells (PBMCs) and platelets from volunteers without known metabolic pathology and patients with mitochondrial disease. Oxygen consumption rates were evaluated and respiratory parameters indicative of mitochondrial function were obtained.

A negative correlation between age and respiratory parameters of PBMCs from control individuals was observed. Surprisingly, respiratory parameters of PBMCs normalized by cell number were similar in patients and young controls. Considering possible compensatory mechanisms, mtDNA copy number in PBMCs was quantified and an increase was found in patients with respect to controls. Hence, respiratory parameters normalized by mtDNA copy number were determined, and in these conditions a decrease in maximum respiration rate and spare respiratory capacity was observed in patients relative to control individuals.

In platelets no decay was seen in mitochondrial function with age, while a reduction in basal, ATP-independent and ATP-dependent respiration normalized by cell number was detected in patients compared to control subjects.

In summary, our results offer promising perspectives regarding the assessment of mitochondrial function in blood cells for the diagnosis of mitochondrial disease, minimizing the need for invasive procedures such as muscle biopsies, and for following disease progression and response to treatments.

人类线粒体疾病是由线粒体 (mtDNA) 或核 DNA 突变引起的氧化磷酸化缺陷引起的一组异质性疾病。线粒体疾病的诊断具有挑战性，因为多个基因的突变会影响线粒体功能，临床变异性很大，基因型和表型之间的相关性较差。在这里，我们评估了来自没有已知代谢病理学的志愿者和患有线粒体疾病的患者的外周血单个核细胞 (PBMC) 和血小板中的线粒体功能。评估耗氧率并获得指示线粒体功能的呼吸参数。

观察到来自对照个体的 PBMC 的年龄和呼吸参数之间存在负相关。令人惊讶的是，通过细胞数标准化的 PBMC 的呼吸参数在患者和年轻对照中相似。考虑到可能的补偿机制，对 PBMC 中的 mtDNA 拷贝数进行了量化，并且发现患者中的 mtDNA 拷贝数相对于对照组有所增加。因此，确定了由 mtDNA 拷贝数标准化的呼吸参数，并且在这些条件下，观察到患者相对于对照个体的最大呼吸速率和备用呼吸能力降低。

在血小板中，没有观察到线粒体功能随着年龄的增长而衰减，而与对照受试者相比，在患者中检测到由细胞数量标准化的基础、不依赖 ATP 和依赖 ATP 的呼吸减少。

总之，我们的结果为评估血细胞中的线粒体功能以诊断线粒体疾病、最大限度地减少对肌肉活检等侵入性手术的需求以及跟踪疾病进展和对治疗的反应提供了有希望的前景。