Mitochondrial resetting and metabolic reprogramming in induced pluripotent stem cells and mitochondrial disease modeling

• Published in: Biochimica et biophysica acta Vol. 1860; no. 4; pp. 686 - 693
• Main Authors: Hsu, Yi-Chao, Chen, Chien-Tsun, Wei, Yau-Huei
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2016
• Subjects: Animals; cardiomyocytes; Cellular Reprogramming; drugs; embryonic stem cells; energy; fibroblasts; Glycolysis; Humans; Induced pluripotent stem cells; Induced Pluripotent Stem Cells - metabolism; Induced Pluripotent Stem Cells - pathology; Metabolic reprogramming; mitochondria; Mitochondria - genetics; Mitochondria - metabolism; Mitochondria - pathology; Mitochondrial disease; Mitochondrial Diseases - genetics; Mitochondrial Diseases - metabolism; Mitochondrial Diseases - pathology; mitochondrial DNA; Models, Biological; oxidative phosphorylation; patients; screening; somatic cells; transcription factors; Glycolysis; Metabolic reprogramming; Induced pluripotent stem cells; Mitochondrial disease
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2016.01.009

Nuclear reprogramming with pluripotency factors enables somatic cells to gain the properties of embryonic stem cells. Mitochondrial resetting and metabolic reprogramming are suggested to be key early events in the induction of human skin fibroblasts to induced pluripotent stem cells (iPSCs). We review recent advances in the study of the molecular basis for mitochondrial resetting and metabolic reprogramming in the regulation of the formation of iPSCs. In particular, the recent progress in using iPSCs for mitochondrial disease modeling was discussed. iPSCs rely on glycolysis rather than oxidative phosphorylation as a major supply of energy. Mitochondrial resetting and metabolic reprogramming thus play crucial roles in the process of generation of iPSCs from somatic cells. Neurons, myocytes, and cardiomyocytes are cells containing abundant mitochondria in the human body, which can be differentiated from iPSCs or trans-differentiated from fibroblasts. Generating these cells from iPSCs derived from skin fibroblasts of patients with mitochondrial diseases or by trans-differentiation with cell-specific transcription factors will provide valuable insights into the role of mitochondrial DNA heteroplasmy in mitochondrial disease modeling and serves as a novel platform for screening of drugs to treat patients with mitochondrial diseases. •Mitochondrial resetting and metabolic reprogramming are suggested to be the key events in the induction of human skin fibroblasts to induced pluripotent stem cells (iPSCs).•iPSCs rely on glycolysis rather than oxidative phosphorylation as a major source of energy.•Mitochondrial resetting and metabolic reprogramming play a crucial role in the process of generation of iPSCs from somatic cells.•Formation and functions of iPSCs can therefore be manipulated by factors or agents that act on the biogenesis or oxidative phosphorylation system of mitochondria.