An MTCH2 Pathway Repressing Mitochondria Metabolism Regulates Haematopoietic Stem Cell Fate

Overview

Journal Nat Commun

Specialty Biology

Date 2015 Jul 30

PMID 26219591

Citations 119

Authors

Maria Maryanovich

Yehudit Zaltsman

Antonella Ruggiero

Andres Goldman

Liat Shachnai

Smadar Levin Zaidman

Ziv Porat

Karin Golan

Tsvee Lapidot

Atan Gross

Affiliations

Soon will be listed here.

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.

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