Mohrin Mary, Chen Danica
aProgram in Metabolic Biology, Nutritional Sciences and Toxicology, University of California bCalico Life Sciences, South San Francisco, California, USA.
Curr Opin Hematol. 2016 Jul;23(4):318-24. doi: 10.1097/MOH.0000000000000244.
Cell-cycle checkpoints are surveillance mechanisms in eukaryotic cells that monitor the condition of the cell, repair cellular damages, and allow the cell to progress through the various phases of the cell cycle when conditions become favorable. We review recent advances in hematopoietic stem cell (HSC) biology, highlighting a mitochondrial metabolic checkpoint that is essential for HSCs to return to the quiescent state.
As quiescent HSCs enter the cell cycle, mitochondrial biogenesis is induced, which is associated with increased mitochondrial protein folding stress and mitochondrial oxidative stress. Mitochondrial unfolded protein response and mitochondrial oxidative stress response are activated to alleviate stresses and allow HSCs to exit the cell cycle and return to quiescence. Other mitochondrial maintenance mechanisms include mitophagy and asymmetric segregation of aged mitochondria.
Because loss of HSC quiescence results in the depletion of the HSC pool and compromised tissue regeneration, deciphering the molecular mechanisms that regulate the mitochondrial metabolic checkpoint in HSCs will increase our understanding of hematopoiesis and how it becomes dysregulated under pathological conditions and during aging. More broadly, this knowledge is instrumental for understanding the maintenance of cells that convert between quiescence and proliferation to support their physiological functions.
细胞周期检查点是真核细胞中的监测机制，可监测细胞状况、修复细胞损伤，并在条件适宜时使细胞顺利通过细胞周期的各个阶段。我们综述了造血干细胞（HSC）生物学的最新进展，重点介绍了一个对HSC恢复静止状态至关重要的线粒体代谢检查点。
当静止的HSC进入细胞周期时，线粒体生物合成被诱导，这与线粒体蛋白折叠应激和线粒体氧化应激增加有关。线粒体未折叠蛋白反应和线粒体氧化应激反应被激活，以减轻应激，使HSC退出细胞周期并恢复静止状态。其他线粒体维持机制包括线粒体自噬和老化线粒体的不对称分离。
由于HSC静止状态的丧失会导致HSC池的耗竭和组织再生受损，破译调节HSC中线粒体代谢检查点的分子机制将增进我们对造血作用以及在病理条件下和衰老过程中造血作用如何失调的理解。更广泛地说，这些知识有助于理解在静止和增殖之间转换以支持其生理功能的细胞的维持。
