Mitochondrial Deep Dive into Hematopoietic Stem Cell Dormancy: Not Much Glycolysis but Plenty of Sluggish Lysosomes

The discovery of hematopoietic stem cells (HSCs) heterogeneity has had major implications for investigations of hematopoietic stem cell disorders, clonal hematopoiesis, and HSC aging. More recent studies of the heterogeneity of HSCs' organelles have begun to provide additional insights into HSCs' behavior with far-reaching ramifications for the mechanistic understanding of aging of HSCs and stem cell-derived diseases. Mitochondrial heterogeneity has been explored to expose HSC subsets with distinct properties and functions. Here we review some of the recent advances in these lines of studies that challenged the classic view of glycolysis in HSCs and led to the identification of lysosomes as dynamic pivotal switches in controlling HSC quiescence versus activation beyond their function in autophagy.