摘要
Mitochondrion is a semi-autonomous organelle,important for cell energy metabolism,apoptosis,the production of reactive oxygen species(ROS),and Ca2+homeostasis.Mitochondrial DNA(mtDNA)mutation is one of the primary factors in mitochondrial disorders.Though much progress has been made,there remain many difficulties in constructing cell models for mitochondrial diseases.This seriously restricts studies related to targeted drug discovery and the mechanism and therapy for such diseases.Here we summarize the characteristics of patient-specific immortalized lymphoblastoid cells,fibroblastoid cells,cytoplasmic hybrid(cybrid)cell lines,and induced pluripotent stem cells(iPSCs)-derived differentiation cells in the study of mitochondrial disorders,as well as offering discussion of roles and advances of these cell models,particularly in the screening of drugs.
线粒体是一种半自主性细胞器,不仅是细胞能量代谢的重要场所,而且与细胞凋亡、活性氧(ROS)产生和Ca^(2+)稳态等密切相关。线粒体DNA(mtDNA)突变是线粒体疾病发生的重要原因。当前,线粒体疾病细胞模型构建仍存在许多困难,严重制约线粒体疾病的致病机制、靶向药物筛选和临床治疗等研究。本文将重点介绍线粒体疾病细胞模型的构建和特征,包括患者特异性永生化淋巴细胞模型、成纤维细胞模型及其衍生的转线粒体细胞模型和诱导多能干细胞及其定向分化细胞模型,以及这些细胞模型在线粒体药物筛选中的作用和研究进展。
作者
Shuang-yi HU
Qian-qian ZHUANG
Yue QIU
Xu-fen ZHU
Qing-feng YAN
Shuang-yi HU;Qian-qian ZHUANG;Yue QIU;Xu-fen ZHU;Qing-feng YAN(Institute of Genetics and Regenerative Biology,College of Life Sciences,Zhejiang University;Department of Pediatrics,the First Affiliated Hospital,School of Medicine,Zhejiang University;Key Laboratory for Cell and Gene Engineering of Zhejiang Province)
基金
Project supported by the National Basic Research Program of China(No.2014CB943001)
the National Natural Science Foundation of China(Nos.31771398 and 31571299)
the Fundamental Research Funds for the Central Universities(No.2019QNA6001)
the Zhejiang Provincial Natural Science Foundation of China(Nos.LZ19C060001 and LY14C060004)
