Centro Andaluz de Biología del Desarrollo, and CIBERER, Instituto de Salud Carlos III, Universidad Pablo de Olavide-CSIC-JA, Carretera de Utrera km1, 41013 Sevilla, Spain.
Centre for Genomics and Oncological Research (GENYO), Avenida de la Ilustración 114, 18016 Granada, Spain.
Int J Mol Sci. 2021 Sep 22;22(19):10211. doi: 10.3390/ijms221910211.
Primary coenzyme Q (CoQ) deficiency includes a heterogeneous group of mitochondrial diseases characterized by low mitochondrial levels of CoQ due to decreased endogenous biosynthesis rate. These diseases respond to CoQ treatment mainly at the early stages of the disease. The advances in the next generation sequencing (NGS) as whole-exome sequencing (WES) and whole-genome sequencing (WGS) have increased the discoveries of mutations in either gene already described to participate in CoQ biosynthesis or new genes also involved in this pathway. However, these technologies usually provide many mutations in genes whose pathogenic effect must be validated. To functionally validate the impact of gene variations in the disease's onset and progression, different cell models are commonly used. We review here the use of yeast strains for functional complementation of human genes, dermal skin fibroblasts from patients as an excellent tool to demonstrate the biochemical and genetic mechanisms of these diseases and the development of human-induced pluripotent stem cells (hiPSCs) and iPSC-derived organoids for the study of the pathogenesis and treatment approaches.
原发性辅酶 Q（CoQ）缺乏症包括一组异质性的线粒体疾病，其特征是由于内源性生物合成率降低，导致线粒体 CoQ 水平降低。这些疾病在疾病的早期阶段主要对 CoQ 治疗有反应。下一代测序（NGS）技术的进步，如全外显子组测序（WES）和全基因组测序（WGS），增加了已经描述的参与 CoQ 生物合成的基因或新基因的突变的发现，这些基因也参与该途径。然而，这些技术通常会在基因中发现许多突变，其致病作用必须得到验证。为了在疾病的发生和进展中功能验证基因变异的影响，通常使用不同的细胞模型。我们在这里回顾了酵母菌株在人类基因功能互补中的应用、患者的皮肤成纤维细胞作为证明这些疾病的生化和遗传机制的极好工具，以及人类诱导多能干细胞（hiPSC）和 iPSC 衍生类器官的发展，用于研究发病机制和治疗方法。
