MiR-31/SDHA Axis Regulates Reprogramming Efficiency through Mitochondrial Metabolism

• Published in: Stem cell reports 2016-07, Vol.7 (1), p.1-10
• Main Authors: Lee, Man Ryul, Mantel, Charlie, Lee, Sang A., Moon, Sung-Hwan, Broxmeyer, Hal E.
• Format: Article
• Language: English
• Subjects: Animals; Cell Differentiation - genetics; Cell Line; Cellular Reprogramming - genetics; Electron Transport Complex II - genetics; Electron Transport Complex II - metabolism; Energy Metabolism - genetics; Humans; Induced Pluripotent Stem Cells - metabolism; Mice; MicroRNAs - genetics; Mitochondria - genetics; Mitochondria - metabolism; Signal Transduction
• ISSN: 2213-6711; 2213-6711
• DOI: 10.1016/j.stemcr.2016.05.012

Metabolism is remodeled when somatic cells are reprogrammed into induced pluripotent stem cells (iPSCs), but the majority of iPSCs are not fully reprogrammed. In a shift essential for reprogramming, iPSCs use less mitochondrial respiration but increased anaerobic glycolysis for bioenergetics. We found that microRNA 31 (miR-31) suppressed succinate dehydrogenase complex subunit A (SDHA) expression, vital for mitochondrial electron transport chain (ETC) complex II. MiR-31 overexpression in partially reprogrammed iPSCs lowered SDHA expression levels and oxygen consumption rates to that of fully reprogrammed iPSCs, but did not increase the proportion of fully reprogrammed TRA1-60+ cells in colonies unless miR-31 was co-transduced with Yamanaka factors, which resulted in a 2.7-fold increase in full reprogramming. Thus switching from mitochondrial respiration to glycolytic metabolism through regulation of the miR-31/SDHA axis is critical for lowering the reprogramming threshold. This is supportive of multi-stage reprogramming whereby metabolic remodeling is fundamental. •The majority of iPSCs are stable and not fully reprogrammed•Regulation of miR-31/SDHA axis lowers reprogramming threshold•Switching from mitochondrial respiration to glycolytic metabolism is critical In this article, Broxmeyer, Lee, and colleagues demonstrate that switching from mitochondrial respiration to glycolytic metabolism through regulation of the miR-31/SDHA axis is critical for lowering the reprogramming threshold. This is supportive of multi-stage reprogramming whereby metabolic remodeling is fundamental.