The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
Mitochondrial calcium exchange links metabolism with the epigenome to control cellular differentiation
Open accessAbstract
Fibroblast to myofibroblast differentiation is crucial for the initial healing response but excessive myofibroblast activation leads to pathological fibrosis. Therefore, it is imperative to understand the mechanisms underlying myofibroblast formation. Here we report that mitochondrial calcium (m Ca 2+) signaling is a regulatory mechanism in myofibroblast differentiation and fibrosis. We demonstrate that fibrotic signaling alters gating of the mitochondrial calcium uniporter (mtCU) in a MICU1-dependent fashion to reduce m Ca 2+ uptake and induce coordinated changes in metabolism, i.e., increased glycolysis feeding anabolic pathways and glutaminolysis yielding increased α-ketoglutarate (αKG) bioavailability. m Ca 2+-dependent metabolic reprogramming leads to the activation of αKG-dependent histone demethylases, enhancing chromatin accessibility in loci specific to the myofibroblast gene program, resulting in differentiation. Our results uncover an important role for the mtCU beyond metabolic regulation and cell death and demonstrate that m Ca 2+ signaling regulates the epigenome to influence cellular differentiation.
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Cites
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From Krebs to clinic: glutamine metabolism to cancer therapy
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Glycolytic Reprogramming in Myofibroblast Differentiation and Lung Fibrosis
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Cited by
Mitochondrial calcium exchange in physiology and disease
Garbincius, J. F., & Elrod, J. W. (2022) · Physiological Reviews · doi:10.1152/physrev.00041.2020 · Cited by 412
Self-citationMaxwell, K. G., Augsornworawat, P., Velazco-Cruz, L., Kim, M. H., Asada, R., Hogrebe, N. J., Morikawa, S., Urano, F., & Millman, J. R. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aax9106 · Cited by 183
HIF-1-Independent Mechanisms Regulating Metabolic Adaptation in Hypoxic Cancer Cells
Lee, S.-H., Golinska, M., & Griffiths, J. R. (2021) · Cells · doi:10.3390/cells10092371 · Cited by 169
Novel insights from a multiomics dissection of the Hayflick limit
Chan, M., Yuan, H., Soifer, I., Maile, T. M., Wang, R. Y., Ireland, A., O'Brien, J. J., Goudeau, J., Chan, L. J., Vijay, T., et al. (2022) · eLife · doi:10.7554/elife.70283 · Cited by 99
“In light of these, replicative senescence resembles a specialized subtype of EMT specific to the trans-differentiation of fibroblasts into myofibroblasts (FMT) in response to wound healing ( Lombardi et al., 2019 ; Gibb et al., 2020 ; Hinz and Lagares, 2020 ).”
Panagopoulos, D., Karabarbounis, A., Yakymenko, I., & Chrousos, G. (2021) · International Journal of Oncology · doi:10.3892/ijo.2021.5272 · Cited by 73
Metadata
- Authors
- Lombardi, A. A., Gibb, A. A., Arif, E., Kolmetzky, D. W., Tomar, D., Luongo, T. S., Jadiya, P., Murray, E. K., Lorkiewicz, P. K., Hajnóczky, G., Murphy, E., Arany, Z. P., Kelly, D. P., Margulies, K. B., Hill, B. G., & Elrod, J. W.
- Venue
- Nature Communications
- Published
- 2019-10-04
- Volume
- 10
- Issue
- 1
- Pages
- 4509-4509
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2977811794
- Cited by
- 160
- References
- 13
- FWCI
- 4.65
- Type
- journal article
- Language
- en
- Open access
- gold
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- CoChat. (2026). Citation check: Mitochondrial calcium exchange links metabolism with the epigenome to control cellular differentiation. https://app.cochat.ai/papers/10.1038/s41467-019-12103-x
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- Lombardi, A. A., Gibb, A. A., Arif, E., Kolmetzky, D. W., Tomar, D., Luongo, T. S., Jadiya, P., Murray, E. K., Lorkiewicz, P. K., Hajnóczky, G., Murphy, E., Arany, Z. P., Kelly, D. P., Margulies, K. B., Hill, B. G., & Elrod, J. W. (2019). Mitochondrial calcium exchange links metabolism with the epigenome to control cellular differentiation. Nature Communications. https://doi.org/10.1038/s41467-019-12103-x
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
