The axis of mTOR-mitochondria-ROS and stemness of the hematopoietic stem cells.
It has been hypothesized that adult hematopoietic stem cells (HSCs) need to remain quiescent to retain their long-term self-renewal activity and multipotency. However, it is still unclear how lack of quiescence is detrimental to HSC. We identified that the mTOR pathway is the key to HSCs quiescence. mTOR overactivation caused increased mitochondrial biogenesis and accumulation of much higher level of reactive oxygen species (ROS). Removal of ROS rescued HSC defects associated with hyperactivated mTOR. We propose susceptibility to ROS as the underlying cause for HSC's general requirement for quiescence.
Chen
Chong
C
Department of Surgery, University of Michigan School of Medicine, 109 Zina Pitcher Place, Ann Arbor, MI 48109, USA.
Liu
Yu
Y
Liu
Yang
Y
Zheng
Pan
P
D000818:Animals; D002453:Cell Cycle; D049109:Cell Proliferation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D017382:Reactive Oxygen Species; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases