The DOI matches its Crossref record; 79 of the 79 references it cites were found in a registry or an index.
Mitochondrial dysfunction remodels one-carbon metabolism in human cells
Open accessAbstract
Mitochondrial dysfunction is associated with a spectrum of human disorders, ranging from rare, inborn errors of metabolism to common, age-associated diseases such as neurodegeneration. How these lesions give rise to diverse pathology is not well understood, partly because their proximal consequences have not been well-studied in mammalian cells. Here we provide two lines of evidence that mitochondrial respiratory chain dysfunction leads to alterations in one-carbon metabolism pathways. First, using hypothesis-generating metabolic, proteomic, and transcriptional profiling, followed by confirmatory experiments, we report that mitochondrial DNA depletion leads to an ATF4-mediated increase in serine biosynthesis and transsulfuration. Second, we show that lesioning the respiratory chain impairs mitochondrial production of formate from serine, and that in some cells, respiratory chain inhibition leads to growth defects upon serine withdrawal that are rescuable with purine or formate supplementation. Our work underscores the connection between the respiratory chain and one-carbon metabolism with implications for understanding mitochondrial pathogenesis.
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Cited by
One-Carbon Metabolism in Health and Disease
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Microglia in Alzheimer’s disease
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The multifaceted contributions of mitochondria to cellular metabolism
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Yang, M., & Vousden, K. H. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.81 · Cited by 992
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Metadata
- Authors
- Bao, X. R., Ong, S.-E., Goldberger, O., Peng, J., Sharma, R., Thompson, D. A., Vafai, S. B., Cox, A. G., Marutani, E., Ichinose, F., Goessling, W., Regev, A., Carr, S. A., Clish, C. B., & Mootha, V. K.
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2016-06-16
- Volume
- 5
- ISSN
- 2050-084X (ISSN-L)
- OpenAlex
- W2439976878
- Cited by
- 448
- References
- 79
- FWCI
- 25.28
- Type
- journal article
- Language
- en
- Open access
- gold
- Licence
- creativecommons.org/licenses/by/4.0/ (vor)
- creativecommons.org/licenses/by/4.0/ (am)
- creativecommons.org/licenses/by/4.0/ (tdm)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (R01DK081457, 2R01CA119176, R01HL101930)
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- Bao, X. R., Ong, S.-E., Goldberger, O., Peng, J., Sharma, R., Thompson, D. A., Vafai, S. B., Cox, A. G., Marutani, E., Ichinose, F., Goessling, W., Regev, A., Carr, S. A., Clish, C. B., & Mootha, V. K. (2016). Mitochondrial dysfunction remodels one-carbon metabolism in human cells. eLife. https://doi.org/10.7554/elife.10575
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