Figure 1

The induction of pluripotency involves the establishment of a cellular state characterized by low levels of oxidative stress. This is accomplished through a global metabolic restructuring which leads to reduced mitochondrial oxidative phosphorylation (OXPHOS) and increased energy flux towards glycolysis and the pentose phosphate pathway (PPP) (orange arrows). However, this glycolytic shift is not adequately sufficient to prevent the increased leakage of reactive oxygen species (ROS) associated with viral-based four factor (4F) reprogramming. This results in DNA damage that may have detrimental consequences on iPSC functionality (red arrows). The paper by Ji et al. demonstrates that the supplementation with ROS-scavenging molecules provides additional defense against redox imbalance, giving rise to iPSCs bearing fewer genomic aberrations (blue arrows).