Swansea University Medical School, Swansea University, Swansea, SA2 8PP, UK.
Mutagenesis. 2023 Jun 20;38(3):132-138. doi: 10.1093/mutage/gead010.
Mitochondrial DNA mutation and toxicity have been linked to several inherited and acquired diseases; however, these are challenging to diagnose and characterize due to clinical and genetic heterogeneity. This review investigates current techniques for the analysis of mitochondrial perturbations, and novel, emerging endpoints for routine application within the clinical setting. Particular focus is given to the biochemistry of the mitochondria influencing each endpoint and the relation of these to toxicity. Current approaches such as the use of metabolic markers (e.g. lactate production), and muscle biopsies to measure mitochondrial proteins were found to lack specificity. Newly emerging identified endpoints were: fibroblast growth factor-21, glucose uptake, mitochondrial membrane potential, mitochondrial morphology, mtDNA heteroplasmy, and mutation of mtDNA and nuclear DNA. Owed to the advancement in genetic analysis techniques, it is suggested by this review that genotypic endpoints of mtDNA mutation and heteroplasmy show particular promise as indicators of mitochondrial disease. It is, however, acknowledged that any single endpoint in isolation offers limited information; therefore, it is recommended that analysis of several endpoints simultaneously will offer the greatest benefit in terms of disease diagnosis and study. It is hoped that this review further highlights the need for advancement in understanding mitochondrial disease.
线粒体 DNA 突变和毒性与几种遗传和获得性疾病有关；然而，由于临床和遗传异质性，这些疾病的诊断和特征描述具有挑战性。本综述研究了目前分析线粒体扰动的技术，以及新出现的、常规应用于临床环境的新兴终点。特别关注影响每个终点的线粒体生物化学以及这些终点与毒性的关系。发现当前的方法，如使用代谢标志物（例如乳酸生成）和肌肉活检来测量线粒体蛋白，缺乏特异性。新出现的确定的终点是：成纤维细胞生长因子 21、葡萄糖摄取、线粒体膜电位、线粒体形态、mtDNA 异质性以及 mtDNA 和核 DNA 的突变。由于遗传分析技术的进步，本综述认为 mtDNA 突变和异质性的基因型终点作为线粒体疾病的指标具有特殊的前景。然而，需要承认的是，任何单一终点孤立地提供的信息都很有限；因此，建议同时分析几个终点将在疾病诊断和研究方面提供最大的益处。希望本综述进一步强调了加深对线粒体疾病理解的必要性。
