An MTCH2 pathway repressing mitochondria metabolism regulates haematopoietic stem cell fate

Maria Maryanovich, Yoav Zaltsman, Antonella Ruggiero, Andres Goldman, Liat Shachnai, Ziv Porat, Karin Golan, Atan Gross, Smadar Levin Zaidman, Tsvee Lapidot

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number7901
JournalNature Communications
Volume6
DOIs
StatePublished - 29 Jul 2015

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General
  • General Biochemistry,Genetics and Molecular Biology
  • General Physics and Astronomy

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