The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Nuclear Localization of Mitochondrial TCA Cycle Enzymes as a Critical Step in Mammalian Zygotic Genome Activation
Open accessAbstract
SUMMARY Transcriptional control requires epigenetic changes directed by mitochondrial tricarboxylic acid (TCA) cycle metabolites. In the mouse embryo, global epigenetic changes occur during the zygotic genome activation (ZGA) at a 2-cell stage. Pyruvate is essential for development beyond this stage, which is at odds with the low activity of mitochondria in this period. We now show that a number of enzymatically active mitochondrial enzymes associated with the TCA cycle essential for epigenetic remodeling are transiently and partially localized to the nucleus. Pyruvate is essential for this nuclear localization, and a failure of TCA cycle enzymes to enter the nucleus correlates with loss of specific histone modifications and a block in ZGA. At later stages, however, these enzymes are exclusively mitochondrial. In humans, the enzyme pyruvate dehydrogenase is transiently nuclear at the 4/8-cell stage coincident with timing of human embryonic genome activation, suggesting a conserved metabolic control mechanism underlying early pre-implantation development.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Xiao, M., Yang, H., Xu, W., Ma, S., Lin, H., Zhu, H., Liu, L., Liu, Y., Yang, C., Xu, Y., et al. (2012) · Genes & Development · doi:10.1101/gad.191056.112 · Cited by 1,188
Classical Nuclear Localization Signals: Definition, Function, and Interaction with Importin α
Lange, A., Mills, R. E., Lange, C. J., Stewart, M., Devine, S. E., & Corbett, A. H. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.r600026200 · Cited by 1,146
Genetic programs in human and mouse early embryos revealed by single-cell RNA sequencing
Xue, Z., Huang, K., Cai, C., Cai, L., Jiang, C.-Y., Feng, Y., Liu, Z., Zeng, Q., Cheng, L., Sun, Y. E., et al. (2013) · Nature · doi:10.1038/nature12364 · Cited by 963
A new pathway for mitochondrial quality control: Mitochondrial-derived vesicles
Sugiura, A., McLelland, G., Fon, E. A., & McBride, H. M. (2014) · The EMBO Journal · doi:10.15252/embj.201488104 · Cited by 862
The pattern of energy metabolism in the mouse oöcyte and zygote.
Biggers, J. D., Whittingham, D. G., & Donahue, R. P. (1967) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.58.2.560 · Cited by 697
Sutendra, G., Kinnaird, A., Dromparis, P., Paulin, R., Stenson, T. H., Haromy, A., Hashimoto, K., Zhang, N., Flaim, E., & Michelakis, E. D. (2014) · Cell · doi:10.1016/j.cell.2014.04.046 · Cited by 648
Aoki, F., Worrad, D. M., & Schultz, R. M. (1997) · Developmental Biology · doi:10.1006/dbio.1996.8466 · Cited by 612
Regulation of zygotic gene activation in the mouse
Schultz, R. M. (1993) · BioEssays · doi:10.1002/bies.950150806 · Cited by 575
Maternal control of early mouse development
Li, L., Zheng, P., & Dean, J. (2010) · Development · doi:10.1242/dev.039487 · Cited by 481
Regulation of pyruvate dehydrogenase complex activity by reversible phosphorylation
Holness, M. J., & Sugden, M. C. (2003) · Biochemical Society Transactions · doi:10.1042/bst0311143 · Cited by 479
Cited by
The evolving metabolic landscape of chromatin biology and epigenetics
Dai, Z., Ramesh, V., & Locasale, J. W. (2020) · Nature Reviews Genetics · doi:10.1038/s41576-020-0270-8 · Cited by 494
Spatiotemporal Control of Acetyl-CoA Metabolism in Chromatin Regulation
Sivanand, S., Viney, I., & Wellen, K. E. (2018) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2017.11.004 · Cited by 357
Metabolic signatures of cancer cells and stem cells
Intlekofer, A. M., & Finley, L. W. S. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0032-0 · Cited by 322
Acetyl-CoA metabolism in cancer
Guertin, D. A., & Wellen, K. E. (2023) · Nature Reviews Cancer · doi:10.1038/s41568-022-00543-5 · Cited by 303
Lactate as a myokine and exerkine: drivers and signals of physiology and metabolism
Brooks, G. A., Osmond, A. D., Arevalo, J. A., Duong, J. J., Curl, C. C., Moreno-Santillan, D. D., & Leija, R. G. (2023) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00497.2022 · Cited by 171
Metadata
- Authors
- Nagaraj, R., Sharpley, M. S., Chi, F., Braas, D., Zhou, Y., Kim, R., Clark, A. T., & Banerjee, U.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2017-01
- Volume
- 168
- Issue
- 1-2
- Pages
- 210-223.e11
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2578505993
- Cited by
- 355
- References
- 34
- FWCI
- 8.25
- Type
- journal article
- Language
- en
- Open access
- bronze
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Nuclear Localization of Mitochondrial TCA Cycle Enzymes as a Critical Step in Mammalian Zygotic Genome Activation. https://app.cochat.ai/papers/10.1016/j.cell.2016.12.026
- The paper
- Nagaraj, R., Sharpley, M. S., Chi, F., Braas, D., Zhou, Y., Kim, R., Clark, A. T., & Banerjee, U. (2017). Nuclear Localization of Mitochondrial TCA Cycle Enzymes as a Critical Step in Mammalian Zygotic Genome Activation. Cell. https://doi.org/10.1016/j.cell.2016.12.026
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
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.
