An MTCH2 pathway repressing mitochondria metabolism regulates haematopoietic stem cell fate

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

Research output: Contribution to journalArticle

71 Citations (Scopus)

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 (US)
Article number7901
JournalNature communications
Volume6
DOIs
StatePublished - Jul 29 2015

Fingerprint

phosphorylation
Mitochondria
mitochondria
stem cells
Oxidative Phosphorylation
metabolism
Hematopoietic Stem Cells
Stem cells
Metabolism
Reactive Oxygen Species
adenosine triphosphate
entry
Adenosine Triphosphate
Irradiation
Mitochondrial Size
oxygen
glycolysis
Phosphorylation
homeostasis
Glycolysis

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Maryanovich, M., Zaltsman, Y., Ruggiero, A., Goldman, A., Shachnai, L., Zaidman, S. L., ... Gross, A. (2015). An MTCH2 pathway repressing mitochondria metabolism regulates haematopoietic stem cell fate. Nature communications, 6, [7901]. https://doi.org/10.1038/ncomms8901

An MTCH2 pathway repressing mitochondria metabolism regulates haematopoietic stem cell fate. / Maryanovich, Maria; Zaltsman, Yehudit; Ruggiero, Antonella; Goldman, Andres; Shachnai, Liat; Zaidman, Smadar Levin; Porat, Ziv; Golan, Karin; Lapidot, Tsvee; Gross, Atan.

In: Nature communications, Vol. 6, 7901, 29.07.2015.

Research output: Contribution to journalArticle

Maryanovich, M, Zaltsman, Y, Ruggiero, A, Goldman, A, Shachnai, L, Zaidman, SL, Porat, Z, Golan, K, Lapidot, T & Gross, A 2015, 'An MTCH2 pathway repressing mitochondria metabolism regulates haematopoietic stem cell fate', Nature communications, vol. 6, 7901. https://doi.org/10.1038/ncomms8901
Maryanovich, Maria ; Zaltsman, Yehudit ; Ruggiero, Antonella ; Goldman, Andres ; Shachnai, Liat ; Zaidman, Smadar Levin ; Porat, Ziv ; Golan, Karin ; Lapidot, Tsvee ; Gross, Atan. / An MTCH2 pathway repressing mitochondria metabolism regulates haematopoietic stem cell fate. In: Nature communications. 2015 ; Vol. 6.
@article{2248c551cb3c4d31b381b79d35eddca2,
title = "An MTCH2 pathway repressing mitochondria metabolism regulates haematopoietic stem cell fate",
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.",
author = "Maria Maryanovich and Yehudit Zaltsman and Antonella Ruggiero and Andres Goldman and Liat Shachnai and Zaidman, {Smadar Levin} and Ziv Porat and Karin Golan and Tsvee Lapidot and Atan Gross",
year = "2015",
month = "7",
day = "29",
doi = "10.1038/ncomms8901",
language = "English (US)",
volume = "6",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - An MTCH2 pathway repressing mitochondria metabolism regulates haematopoietic stem cell fate

AU - Maryanovich, Maria

AU - Zaltsman, Yehudit

AU - Ruggiero, Antonella

AU - Goldman, Andres

AU - Shachnai, Liat

AU - Zaidman, Smadar Levin

AU - Porat, Ziv

AU - Golan, Karin

AU - Lapidot, Tsvee

AU - Gross, Atan

PY - 2015/7/29

Y1 - 2015/7/29

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84938267949&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84938267949&partnerID=8YFLogxK

U2 - 10.1038/ncomms8901

DO - 10.1038/ncomms8901

M3 - Article

C2 - 26219591

AN - SCOPUS:84938267949

VL - 6

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 7901

ER -