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The mitochondrial respiratory chain is essential for haematopoietic stem cell function
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Journal Article
The mitochondrial respiratory chain is essential for haematopoietic stem cell function
2017
Overview
Adult and fetal haematopoietic stem cells (HSCs) display a glycolytic phenotype, which is required for maintenance of stemness; however, whether mitochondrial respiration is required to maintain HSC function is not known. Here we report that loss of the mitochondrial complex III subunit Rieske iron-sulfur protein (RISP) in fetal mouse HSCs allows them to proliferate but impairs their differentiation, resulting in anaemia and prenatal death. RISP-null fetal HSCs displayed impaired respiration resulting in a decreased NAD
+
/NADH ratio. RISP-null fetal HSCs and progenitors exhibited an increase in both DNA and histone methylation associated with increases in 2-hydroxyglutarate (2HG), a metabolite known to inhibit DNA and histone demethylases. RISP inactivation in adult HSCs also impaired respiration resulting in loss of quiescence concomitant with severe pancytopenia and lethality. Thus, respiration is dispensable for adult or fetal HSC proliferation, but essential for fetal HSC differentiation and maintenance of adult HSC quiescence.
Two papers by Liu
et al.
and Ansó
et al.
study the post-transcriptional regulation of mitochondrial factors in erythropoiesis and the role of RISP-mediated mitochondrial respiration in fetal and adult HSC function via metabolites and epigenetic changes.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/31
/ 38
/ 45/91
/ Adult Stem Cells - metabolism
/ Adult Stem Cells - pathology
/ Anemia
/ Animals
/ DNA
/ Electron Transport Complex III - deficiency
/ Electron Transport Complex III - genetics
/ Electron Transport Complex III - metabolism
/ Female
/ Fetal Stem Cells - metabolism
/ Fetal Stem Cells - pathology
/ Fetuses
/ Genotype
/ Hematopoietic Stem Cells - metabolism
/ Hematopoietic Stem Cells - pathology
/ Iron
/ NAD
/ NADH
/ Nicotinamide adenine dinucleotide
/ Sulfur
