Mitochondrial and Reactive Oxygen Species Signaling Coordinate Stem Cell Fate Decisions and Life Long Maintenance.

Significance: Recent discoveries in mitochondrial biology have transformed and further solidified the importance of mitochondria in development, aging, and disease. Within the realm of regenerative and stem cell research, these recent advances have brought forth new concepts that revolutionize our understanding of metabolic and redox states in the establishment of cellular identity and fate decisions. Recent Advances: Mitochondrial metabolism, morphology, and cellular redox states are dynamic characteristics that undergo shifts during stem cell differentiation. Although it was once thought that this was solely because of changing metabolic needs of differentiating cells, it is now clear that these events are driving forces in the regulation of stem cell identity and fate decisions. Critical Issues: Although recent discoveries have placed mitochondrial function and physiological reactive oxygen species (ROS) at the forefront for the regulation of stem cell self-renewal, how this may impact tissue homeostasis and regenerative capacity is poorly understood. In addition, the role of mitochondria and ROS on the maintenance of a stem cell population in many degenerative diseases and during aging is not clear, despite the fact that mitochondrial dysfunction and elevated ROS levels are commonly observed in these conditions. Future Directions: Given the newly established role for mitochondria and ROS in stem cell self-renewal capacity, special attention should now be directed in understanding how this would impact the development and progression of aging and diseases, whereby mitochondrial and ROS defects are a prominent factor. Antioxid. Redox Signal. 28, 1090-1101.