Evidence map›Paper›PMID 24882210›Full record

ArticleMolecular cell2014

Tracing compartmentalized NADPH metabolism in the cytosol and mitochondria of mammalian cells.

Caroline A Lewis, Seth J Parker, Brian P Fiske, Douglas McCloskey, Dan Y Gui, Courtney R Green, Natalie I Vokes, Adam M Feist, Matthew G Vander Heiden, Christian M Metallo

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 356 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
356citing papers in PubMed, 1 pooled it
27.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

356 citing papers in PubMed, 1 synthesis or guideline pooled it, 579 citations in OpenAlex.

  1. Pooled it
  2. The mitochondrial chaperone HSPD1 folds MTHFD2 independently of its co-chaperone HSPE1.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026
    Article
  3. Article
  4. Review
  5. A Stable Isotope Tracing Primer for the Mass Spectrometrist.Annual review of analytical chemistry (Palo Alto, Calif.) · 2026
    Review
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  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
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  17. Article
  18. Review
  19. Building Localized NADP(H) Recycling Circuits to Advance Enzyme Cascadetronics.Angewandte Chemie (International ed. in English) · 2025
    Article
  20. Article

296 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Caroline A LewisThe Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Seth J ParkerDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Brian P FiskeThe Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Douglas McCloskeyDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Dan Y GuiThe Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Courtney R GreenDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Natalie I VokesThe Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Adam M FeistDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Matthew G Vander HeidenThe Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Dana-Farber Cancer Institute, Boston, MA 02115, USA. Electronic address: mvh@mit.edu.
Christian M MetalloDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Institute of Engineering and Medicine, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: cmetallo@ucsd.edu.
University of California, San Diego · USMassachusetts Institute of Technology · USDana-Farber Cancer Institute · US

Funding

Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
PRE-DOCTORAL TRAINING IN THE BIOLOGICAL SCIENCEST32GM007287 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BELL, STEPHEN P., KEATING, AMY E · 1985 to 2019
$40.8M
Nation Center: Multi-Scale Study- Cellular Networks(RMI)U54CA121852 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2005 to 2015
$37.4M
Training in Multi-Scale Analysis of Biological Structure and FunctionT32EB009380 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrew D. McCulloch, Padmini Rangamani · 2009 to 2026
$4.8M
Regulation of glucose metabolism to allow tumor initiation and growthR01CA168653 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI VANDER HEIDEN, MATTHEW G. · 2013 to 2019
$1.9M
Exploiting Metabloic Defects in Tumors with Mutant IDH1 and IDH2R01CA188652 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI METALLO, CHRISTIAN MICHAEL · 2014 to 2018
$1.6M
Koch Institute Faculty Recruitment for an MD/PHD Physician-ScientistP30CA147882 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI JACKS, TYLER E. · 2009 to 2010
$1.5M
Modeling and analysis of the mechanochemical processes that govern clathrin-mediated endocytosisR01GM132106 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI RANGAMANI, PADMINI · 2020 to 2024
$1.5M
NCI NIH HHS P30 CA147882NCI NIH HHS P30CA147882NCI NIH HHS R01 CA168653NCI NIH HHS R01CA168653NCI NIH HHS R01 CA188652NCI NIH HHS U54 CA121852NCI NIH HHS U54-CA121852-09NIBIB NIH HHS T32 EB009380NIGMS NIH HHS R01 GM132106NIGMS NIH HHS T32 GM007287NIGMS NIH HHS T32 GM007753
6 · The paper itself

Abstract

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.

Indexed as

Cell Line, TumorCytosolGlucoseGlycineHumansIsocitrate DehydrogenaseMetabolic Flux AnalysisMitochondriaNADPSerineGlucoseGlycineIDH1 protein, humanIDH2 protein, humanIsocitrate DehydrogenaseNADPSerine

Identifiers

PMID24882210
PMCPMC4106038
OpenAlexW2031022790

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.