Beyond their canonical role in efficient ATP production through oxidative metabolism, mitochondria are increasingly recognized as critical in defining stem cell function and fate. Implicating a fundamental interplay within the epigenetics of eukaryotic cell systems, the integrity of mitochondria is found vital across the developmental/differentiation spectrum from securing pluripotency maintenance to informing organotypic decisions. This overview will discuss recent progress on examining the plasticity of mitochondria in enabling the execution of programming and reprogramming regimens, as well as the application of nuclear reprogramming and somatic cell nuclear transfer as rescue techniques to generate genetically and functionally corrected pluripotent stem cells from patients with mitochondrial DNA-based disease.
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