The DOI matches its Crossref record; 53 of the 54 references it cites were found in a registry or an index.
Tracing Compartmentalized NADPH Metabolism in the Cytosol and Mitochondria of Mammalian Cells
Open accessAbstract
Eukaryotic cells compartmentalize biochemical processes in different organelles, often relying on metabolic cycles to shuttle reducing equivalents across intracellular membranes. NADPH serves as the electron carrier for the maintenance of redox homeostasis and reductive biosynthesis, with separate cytosolic and mitochondrial pools providing reducing power in each respective location. This cellular organization is critical for numerous functions but complicates analysis of metabolic pathways using available methods. Here we develop an approach to resolve NADP(H)-dependent pathways present within both the cytosol and the mitochondria. By tracing hydrogen in compartmentalized reactions that use NADPH as a cofactor, including the production of 2-hydroxyglutarate by mutant isocitrate dehydrogenase enzymes, we can observe metabolic pathway activity in these distinct cellular compartments. Using this system we determine the direction of serine/glycine interconversion within the mitochondria and cytosol, highlighting the ability of this approach to resolve compartmentalized reactions in intact cells.
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.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Serine can also contribute to NADPH production via the folate cycle, which serves to maintain redox homeostasis and support anabolic reactions (Fan et al., 2014; Lewis et al., 2014; Ye et al., 2014).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Lewis et al., 2014
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
Cancer-associated IDH1 mutations produce 2-hydroxyglutarate
Dang, L., White, D. W., Gross, S., Bennett, B. D., Bittinger, M. A., Driggers, E. M., Fantin, V. R., Jang, H. G., Jin, S., Keenan, M. C., et al. (2009) · Nature · doi:10.1038/nature08617 · Cited by 4,154
Aerobic glycolysis: Meeting the metabolic requirements of cell proliferation
Lunt, S. Y., & Vander Heiden, M. G. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154237 · Cited by 3,057
Association of reactive oxygen species levels and radioresistance in cancer stem cells
Diehn, M., Cho, R. W., Lobo, N. A., Kalisky, T., Dorie, M. J., Kulp, A. N., Qian, D., Lam, J. S., Ailles, L. E., Wong, M., et al. (2009) · Nature · doi:10.1038/nature07733 · Cited by 2,555
Ward, P. S., Patel, J., Wise, D. R., Abdel-Wahab, O., Bennett, B. D., Coller, H. A., Cross, J. R., Fantin, V. R., Hedvat, C. V., Perl, A. E., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.01.020 · Cited by 2,020 · cited 2×
“For instance, compartment-specific metabolic cycling through citrate/aKG (Sazanov and Jackson, 1994; Ward et al., 2010), malate/pyruvate (Jiang et al., 2013; Son et al., 2013), proline (Hagedorn and Phang, 1983; Nilsson et al., 2014), and serine (Tibbetts and Appling, 2010) have been suggested to…”
BackgroundGlutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway
Son, J., Lyssiotis, C. A., Ying, H., Wang, X., Hua, S., Ligorio, M., Perera, R. M., Ferrone, C. R., Mullarky, E., Shyh-Chang, N., et al. (2013) · Nature · doi:10.1038/nature12040 · Cited by 1,990
Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia
Metallo, C. M., Gameiro, P. A., Bell, E. L., Mattaini, K. R., Yang, J., Hiller, K., Jewell, C. M., Johnson, Z. R., Irvine, D. J., Guarente, L., et al. (2012) · Nature · doi:10.1038/nature10602 · Cited by 1,791
Self-citationMetabolite profiling identifies a key role for glycine in rapid cancer cell proliferation
Jain, M., Nilsson, R., Sharma, S., Madhusudhan, N., Kitami, T., Souza, A. L., Kafri, R., Kirschner, M. W., Clish, C. B., & Mootha, V. K. (2012) · Science · doi:10.1126/science.1218595 · Cited by 1,403
Bcl-xL Regulates the Membrane Potential and Volume Homeostasis of Mitochondria
Heiden, M. G. V., Chandel, N. S., Williamson, E. K., Schumacker, P. T., & Thompson, C. B. (1997) · Cell · doi:10.1016/s0092-8674(00)80450-x · Cited by 1,378
AMPK regulates NADPH homeostasis to promote tumour cell survival during energy stress
Jeon, S.-M., Chandel, N. S., & Hay, N. (2012) · Nature · doi:10.1038/nature11066 · Cited by 1,132
Antioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachment
Schafer, Z. T., Grassian, A. R., Song, L., Jiang, Z., Gerhart-Hines, Z., Irie, H. Y., Gao, S., Puigserver, P., & Brugge, J. S. (2009) · Nature · doi:10.1038/nature08268 · Cited by 1,031
Cited by
Sorted by citations
Fundamentals of Cancer Metabolism
DeBerardinis, R. J., & Chandel, N. S. (2016) · Science Advances · doi:10.1126/sciadv.1600200 · Cited by 3,013
One-Carbon Metabolism in Health and Disease
Ducker, G. S., & Rabinowitz, J. D. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2016.08.009 · Cited by 2,239
Understanding the Intersections between Metabolism and Cancer Biology
Heiden, M. G. V., & DeBerardinis, R. J. (2017) · Cell · doi:10.1016/j.cell.2016.12.039 · Cited by 2,369
The PI3K–AKT network at the interface of oncogenic signalling and cancer metabolism
Hoxhaj, G., & Manning, B. D. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-019-0216-7 · Cited by 2,137
The multifaceted contributions of mitochondria to cellular metabolism
Spinelli, J. B., & Haigis, M. C. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0124-1 · Cited by 1,935
Metadata
- Authors
- Lewis, C. A., Parker, S. J., Fiske, B. P., McCloskey, D., Gui, D. Y., Green, C. R., Vokes, N. I., Feist, A. M., Vander Heiden, M. G., & Metallo, C. M.
- Affiliations
- Koch Institute for Integrative Cancer Research At MIT (US)
- University of California San Diego (US)
- Corresponding author
- Metallo, Christian M.
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 55
- Issue
- 2
- Pages
- 253-263
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC4106038
- OpenAlex
- W2031022790
- Cited by
- 562
- References
- 54
- Citations by year
- 2026: 22 · 2025: 26 · 2024: 47 · 2023: 48 · 2022: 56 · 2021: 58 · 2020: 66 · 2019: 54 · 2018: 45 · 2017: 50 · 2016: 47 · 2015: 28 · 2014: 15
- FWCI
- 19.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- U.S. Department of Defense (W81XWH, W81XWH-13)
- Damon Runyon Cancer Research Foundation
- Cancer Research Coordinating Committee
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
- National Institutes of Health (W81XWH, CA121852)
- National Cancer Institute (U54-CA121852-09, U54CA121852, R01CA168653, R01CA188652, P30CA147882)
- National Institute of General Medical Sciences (T32GM007753, R01GM132106, T32GM007287)
- National Institute of Biomedical Imaging and Bioengineering (T32EB009380)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Keywords
- NADPH metabolism, compartmentalized metabolism, mitochondrial metabolism, cytosolic metabolism, 2-hydroxyglutarate, isocitrate dehydrogenase, redox homeostasis, reducing power, metabolic pathway activity, mammalian cells
- MeSH terms
- Cytosol, Glucose, Glycine, Humans, Isocitrate Dehydrogenase, Mitochondria, NADP, Serine, Cell Line, Tumor, Metabolic Flux Analysis
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
