Mitochondrial DNA mutation affects the pluripotency of embryonic stem cells with metabolism modulation

Abstract

Mitochondria are the only organelles other than the nucleus harboring their DNA in mammalian cells. The mitochondrial DNA (mtDNA) mutation is the cause of many serious diseases, which still lack effective therapies. Our previous report showed that mtDNA mutation exacerbates female reproductive aging. However, the regulation of mtDNA mutation on stem cells is still unknown. Herein, we generated embryonic stem cells (ESCs) harboring massive mtDNA mutations without affecting genomic DNA to study the role of mtDNA mutation in pluripotency. The mtDNA mutation impacted the balance of pluripotency and totipotency of ESCs with a metabolism modulation as the down-regulation of oxidative phosphorylation in energy production, followed by a high level of ROS production by mitochondria. This work would shed light on the investigation and treatment of mtDNA mutant diseases.