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An MTCH2 pathway repressing mitochondria metabolism regulates haematopoietic stem cell fate
- Source :
- Nature communications. 6
- Publication Year :
- 2015
-
Abstract
- The metabolic state of stem cells is emerging as an important determinant of their fate. In the bone marrow, haematopoietic stem cell (HSC) entry into cycle, triggered by an increase in intracellular reactive oxygen species (ROS), corresponds to a critical metabolic switch from glycolysis to mitochondrial oxidative phosphorylation (OXPHOS). Here we show that loss of mitochondrial carrier homologue 2 (MTCH2) increases mitochondrial OXPHOS, triggering HSC and progenitor entry into cycle. Elevated OXPHOS is accompanied by an increase in mitochondrial size, increase in ATP and ROS levels, and protection from irradiation-induced apoptosis. In contrast, a phosphorylation-deficient mutant of BID, MTCH2's ligand, induces a similar increase in OXPHOS, but with higher ROS and reduced ATP levels, and is associated with hypersensitivity to irradiation. Thus, our results demonstrate that MTCH2 is a negative regulator of mitochondrial OXPHOS downstream of BID, indispensible in maintaining HSC homeostasis.
- Subjects :
- Blotting, Western
General Physics and Astronomy
Apoptosis
Oxidative phosphorylation
Biology
Mitochondrion
Mitochondrial Size
Real-Time Polymerase Chain Reaction
Mitochondrial Membrane Transport Proteins
Radiation Tolerance
General Biochemistry, Genetics and Molecular Biology
Oxidative Phosphorylation
Colony-Forming Units Assay
Mice
Adenosine Triphosphate
Microscopy, Electron, Transmission
Animals
Glycolysis
Membrane Potential, Mitochondrial
Multidisciplinary
Cell Cycle
Cell Differentiation
General Chemistry
Mitochondrial carrier
Flow Cytometry
Hematopoietic Stem Cells
Cell biology
Hematopoiesis
Mitochondria
Haematopoiesis
Stem cell
Reactive Oxygen Species
BH3 Interacting Domain Death Agonist Protein
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Nature communications
- Accession number :
- edsair.doi.dedup.....458882cef998c5762bcf2711944b6b28