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Nat Commun. 2015 Jul 29;6:7901. doi: 10.1038/ncomms8901.

An MTCH2 pathway repressing mitochondria metabolism regulates haematopoietic stem cell fate.

Author information

1
Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
2
Department of Chemical Research Support, Weizmann Institute of Science, Rehovot 76100, Israel.
3
Department of Biological Services, Weizmann Institute of Science, Rehovot 76100, Israel.
4
Department Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.

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.

PMID:
26219591
DOI:
10.1038/ncomms8901
[Indexed for MEDLINE]

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