期刊
AUTOPHAGY
卷 9, 期 11, 页码 1737-1749出版社
LANDES BIOSCIENCE
DOI: 10.4161/auto.26681
关键词
autophagy; mitochondria; mitophagy; hematopoiesis; hematopoietic stem cells; hematopoietic progenitor cells; quiescence; self-renewal; differentiation; commitment
类别
资金
- National Institutes of Health [HL114697]
- Burroughs Wellcome Fund [1006062.01]
- American Society of Hematology
- American Lebanese Syrian Associated Charities (ALSAC)
Hematopoietic stem cells (HSCs) are inherently quiescent and self-renewing, yet can differentiate and commit to multiple blood cell types. Intracellular mitochondrial content is dynamic, and there is an increase in mitochondrial content during differentiation and lineage commitment in HSCs. HSCs reside in a hypoxic niche within the bone marrow and rely heavily on glycolysis, while differentiated and committed progenitors rely on oxidative phosphorylation. Increased oxidative phosphorylation during differentiation and commitment is not only due to increased mitochondrial content but also due to changes in mitochondrial cytosolic distribution and efficiency. These changes in the intracellular mitochondrial landscape contribute signals toward regulating differentiation and commitment. Thus, a functional relationship exists between the mitochondria in HSCs and the state of the HSCs (i.e., stemness vs. differentiated). This review focuses on how autophagy-mediated mitochondrial clearance (i.e., mitophagy) may affect HSC mitochondrial content, thereby influencing the fate of HSCs and maintenance of hematopoietic homeostasis.
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