Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, 465 Kajii cho, Kamigyo ku, Kyoto, 602-8566, Japan.
Department of Regenerative Medicine, Kyoto Prefectural University of Medicine, 465 Kajii cho, Kamigyo ku, Kyoto, 602-8566, Japan.
Sci Rep. 2021 May 25;11(1):10897. doi: 10.1038/s41598-021-90316-1.
Mitochondrial diseases currently have no cure regardless of whether the cause is a nuclear or mitochondrial genome mutation. Mitochondrial dysfunction notably affects a wide range of disorders in aged individuals, including neurodegenerative diseases, cancers, and even senescence. Here, we present a procedure to generate mitochondrial DNA-replaced somatic cells with a combination of a temporal reduction in endogenous mitochondrial DNA and coincubation with exogeneous isolated mitochondria. Heteroplasmy in mitochondrial disease patient-derived fibroblasts in which the mutant genotype was dominant over the wild-type genotype was reversed. Mitochondrial disease patient-derived fibroblasts regained respiratory function and showed lifespan extension. Mitochondrial membranous components were utilized as a vehicle to deliver the genetic materials into endogenous mitochondria-like horizontal genetic transfer in prokaryotes. Mitochondrial DNA-replaced cells could be a resource for transplantation to treat maternal inherited mitochondrial diseases.
无论病因是核基因组还是线粒体基因组突变，目前都没有治愈线粒体疾病的方法。线粒体功能障碍显著影响了老年人的多种疾病，包括神经退行性疾病、癌症，甚至衰老。在这里，我们提出了一种通过暂时减少内源性线粒体 DNA 并与外源性分离的线粒体共孵育来产生线粒体 DNA 替换体体细胞的方法。在突变基因型占优势于野生型基因型的线粒体疾病患者来源的成纤维细胞中，异质性得到了逆转。线粒体疾病患者来源的成纤维细胞恢复了呼吸功能并显示出寿命延长。线粒体膜成分被用作载体将遗传物质递送到类似于原核生物中的内源性线粒体的水平基因转移。线粒体 DNA 替换细胞可能成为治疗母系遗传线粒体疾病的移植资源。
