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An MTCH2 pathway repressing mitochondria metabolism regulates haematopoietic stem cell fate

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  • Maria Maryanovich

    (Weizmann Institute of Science
    Present address: Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research & Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.)

  • Yehudit Zaltsman

    (Weizmann Institute of Science)

  • Antonella Ruggiero

    (Weizmann Institute of Science)

  • Andres Goldman

    (Weizmann Institute of Science)

  • Liat Shachnai

    (Weizmann Institute of Science)

  • Smadar Levin Zaidman

    (Weizmann Institute of Science)

  • Ziv Porat

    (Weizmann Institute of Science)

  • Karin Golan

    (Weizmann Institute of Science)

  • Tsvee Lapidot

    (Weizmann Institute of Science)

  • Atan Gross

    (Weizmann Institute of Science)

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.

Suggested Citation

  • Maria Maryanovich & Yehudit Zaltsman & Antonella Ruggiero & Andres Goldman & Liat Shachnai & Smadar Levin Zaidman & Ziv Porat & Karin Golan & Tsvee Lapidot & Atan Gross, 2015. "An MTCH2 pathway repressing mitochondria metabolism regulates haematopoietic stem cell fate," Nature Communications, Nature, vol. 6(1), pages 1-9, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8901
    DOI: 10.1038/ncomms8901
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