Evidence map›Paper›PMID 40441152›Full record

ArticleMolecular cell2025

Structural and systems characterization of phosphorylation on metabolic enzymes identifies sex-specific metabolic reprogramming in obesity.

Tigist Y Tamir, Shreya Chaudhary, Annie X Li, Sonia E Trojan, Cameron T Flower, Paula Vo, Yufei Cui, Jeffrey C Davis, Rachit Mukkamala, Francesca N Venditti and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Tigist Y TamirKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Center for Precision Cancer Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: tytamir@med.unc.edu.
Shreya ChaudharyKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Annie X LiKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Sonia E TrojanKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA; Faculty of Medicine, Chair of Medical Biochemistry, Jagiellonian University Medical College, Krakow, Poland.
Cameron T FlowerKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Center for Precision Cancer Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA; Program in Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Paula VoProgram in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Yufei CuiKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Jeffrey C DavisKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Rachit MukkamalaKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Francesca N VendittiKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Alissandra L HillisDepartment of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Alex TokerDepartment of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Matthew G Vander HeidenKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Center for Precision Cancer Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA; Dana-Farber Cancer Institute, Boston, MA, USA.
Jessica B SpinelliProgram in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Norman J KennedyProgram in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Roger J DavisProgram in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Forest M WhiteKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Center for Precision Cancer Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; Program in Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: fwhite@mit.edu.

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Jacqueline A. Lees · 1985 to 2026
$93.9M
National Metabolomics Data Repository - nextgen Metabolomics WorkbenchU2CDK119886 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SUBRAMANIAM, SHANKAR · 2018 to 2021
$12.7M
Quantitative systems biology of glioblastoma cells and their interactions with the neuronal and immunological milieuU54CA283114 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Forest M White · 2023 to 2026
$9.7M
Discovery, Regulation and Function of the PI 3-Kinase and AKT Pathway in CancerR35CA253097 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Alex Toker · 2020 to 2026
$6.9M
Understanding the role of metabolism in cancerR35CA242379 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI VANDER HEIDEN, MATTHEW G. · 2019 to 2025
$5.8M
Graduate Training in Computational and Systems BiologyT32GM087237 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BURGE, CHRISTOPHER B · 2009 to 2023
$4.6M
Adipose Tissue Metabolic Stress ResponsesR01DK112698 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI DAVIS, ROGER J. · 2017 to 2025
$4.4M
Metabolic Stress SignalingR01DK107220 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI DAVIS, ROGER J. · 2016 to 2023
$3.6M
Biomedical Data Commons Workbench (BDCW)OT2OD030544 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SUBRAMANIAM, SHANKAR · 2020 to 2024
$3.2M
Identification of adaptive response mechanisms in breast cancer by information theory and proteomicsU01CA238720 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI KRAVCHENKO-BALASHA, NATALY, WHITE, FOREST M · 2019 to 2023
$2.0M
Regulation of oxidative stress signaling by tyrosine phosphorylation of antioxidant enzymesR00GM152834 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Tigist Y Tamir · 2025 to 2026
$498k
Regulation of oxidative stress signaling by tyrosine phosphorylation of antioxidant enzymesK99GM152834 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI TAMIR, TIGIST Y · 2023 to 2024
$175k
NCI NIH HHS P30 CA014051NCI NIH HHS R35 CA242379NCI NIH HHS R35 CA253097NCI NIH HHS U01 CA238720NCI NIH HHS U54 CA283114NICHD NIH HHS F32 HD108930NIDDK NIH HHS R01 DK107220NIDDK NIH HHS R01 DK112698NIDDK NIH HHS U2C DK119886NIGMS NIH HHS K99 GM152834NIGMS NIH HHS R00 GM152834NIGMS NIH HHS T32 GM087237NIH HHS OT2 OD030544
6 · The paper itself

Abstract

Coordination of adaptive metabolism through signaling networks is essential for cellular bioenergetics and homeostasis. Phosphorylation of metabolic enzymes provides a rapid, efficient, and dynamic mechanism to regulate metabolic networks. Our structural analysis stratified phosphosites on metabolic enzymes based on proximity to functional and dimerization domains. Most phosphosites occur on oxidoreductases and are enriched near substrate, cofactor, active sites, or dimer interfaces. Despite low stoichiometry, phosphotyrosine (pY) is overrepresented in functional domains. Using high-fat diet (HFD)-induced obesity in C57BL/6J mice and multiomics, we measured HFD-induced sex-specific dysregulation of pY and metabolites, which was reversible with the antioxidant butylated hydroxyanisole (BHA). Computational modeling revealed predictive pY sites for HFD- or BHA-induced metabolite changes. We characterized functional roles for predictive pY sites on glutathione S-transferase pi 1 (GSTP1), isocitrate dehydrogenase 1 (IDH1), and uridine monophosphate synthase (UMPS) using CRISPR interference (CRISPRi) rescue and stable isotope tracing. Our findings reveal mechanisms whereby cellular signaling fine-tunes enzyme activity and metabolism.

Indexed as

ObesityAnimalsDiet, High-FatEnergy MetabolismFemaleHumansIsocitrate DehydrogenaseMaleMetabolic ReprogrammingMiceMice, Inbred C57BLPhosphorylationSex FactorsSignal TransductionIsocitrate Dehydrogenasecell signalingcomputational modellingGSTP1IDH1metabolismmetabolomicsobesityoxidative stress responsephosphoproteomicsUMPS

Identifiers

PMID40441152
PMCPMC12147527

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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.