The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
An MTCH2 pathway repressing mitochondria metabolism regulates haematopoietic stem cell fate
Open accessAbstract
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. Changes in the metabolic state of stem cells can trigger a shift from quiescence into cell cycle entry. Here Maryanovichet al. identify mitochondrial carrier homolog 2 (MCH2) as a negative regulator of mitochondrial oxidative phosphorylation in haematopoietic stem cells, maintaining their homeostasis.
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Cites
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Self-citationMetabolic regulation of stem cell function in tissue homeostasis and organismal ageing
Chandel, N. S., Jasper, H., Ho, T. T., & Passegué, E. (2016) · Nature Cell Biology · doi:10.1038/ncb3385 · Cited by 326
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Metadata
- Authors
- Maryanovich, M., Zaltsman, Y., Ruggiero, A., Goldman, A., Shachnai, L., Zaidman, S. L., Porat, Z., Golan, K., Lapidot, T., & Gross, A.
- Venue
- Nature Communications
- Published
- 2015-07-29
- Volume
- 6
- Issue
- 1
- Pages
- 7901-7901
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2266362809
- Cited by
- 242
- References
- 12
- FWCI
- 14.02
- Type
- journal article
- Language
- en
- Open access
- gold
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- Maryanovich, M., Zaltsman, Y., Ruggiero, A., Goldman, A., Shachnai, L., Zaidman, S. L., Porat, Z., Golan, K., Lapidot, T., & Gross, A. (2015). An MTCH2 pathway repressing mitochondria metabolism regulates haematopoietic stem cell fate. Nature Communications. https://doi.org/10.1038/ncomms8901
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