Mitochondrial metabolism and the maintenance of hematopoietic stem cell quiescence.

Abstract

Hematopoietic stem cells (HSCs) are characterized by a potent multilineage regenerative capability that is dependent on their quiescence property. In the past few decades, researchers have found many intrinsic and niche-derived factors that can regulate HSCs, whereas how to precisely control HSC behaviors remains elusive. Recently, mitochondrial metabolism has been shown to be involved in the regulation of HSC biology. The purpose of this review is to overview recent advances in the relationship between mitochondrial metabolism and maintenance of HSC quiescence. On the basis of fact that HSCs are heterogeneous populations that have their unique metabolic characteristics, increasing studies have demonstrated that the quiescence and function of HSCs are closely correlated with the mitochondrial mass and activity, as well as the levels of mitochondria-derived reactive oxygen species and metabolites. Apart from that, mitochondria have been reported to undergo internal protective programs, including mitochondrial unfolded protein response, autophagy and mitochondrial dynamics, which are beneficial to maintaining HSC homeostasis. The maintenance of HSC quiescence needs a metabolic balance in mitochondria, and unraveling the metabolic complexity may provide deep understanding of the functional heterogeneity of HSCs.