Evidence map›Paper›PMID 42600612›Full record

ArticleCell2026

Polyamines buffer labile iron to suppress ferroptosis.

Pushkal Sharma, Heather R Keys, Ryan P Mansell, Jillian Stark, Louisa Girard, Christalyn Ausler, Rachel Anderson, Sebastian Müller, Shinya Imada, Ivan S Pires and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors.

Pushkal SharmaWhitehead Institute for Biomedical Research, Cambridge, MA, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Heather R KeysWhitehead Institute for Biomedical Research, Cambridge, MA, USA.
Ryan P MansellDepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA; Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA, USA.
Jillian StarkDepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA; Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA, USA.
Louisa GirardDepartment of Biochemistry, Brandeis University, Waltham, MA, USA.
Christalyn AuslerWhitehead Institute for Biomedical Research, Cambridge, MA, USA.
Rachel AndersonWhitehead Institute for Biomedical Research, Cambridge, MA, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Sebastian MüllerInstitut Curie, CNRS, INSERM, PSL Research University, Paris, France.
Shinya ImadaKoch Institute for Integrative Cancer Research at MIT, Cambridge, MA, USA.
Ivan S PiresDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA, USA.
Tenzin KunchokWhitehead Institute for Biomedical Research, Cambridge, MA, USA.
Millenia WaiteWhitehead Institute for Biomedical Research, Cambridge, MA, USA.
Bingbing YuanWhitehead Institute for Biomedical Research, Cambridge, MA, USA.
Amy DeikBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Luke FerroWhitehead Institute for Biomedical Research, Cambridge, MA, USA.
Paula T HammondDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA, USA.
Raphaël RodriguezInstitut Curie, CNRS, INSERM, PSL Research University, Paris, France.
Maria-Eirini PandeliaDepartment of Biochemistry, Brandeis University, Waltham, MA, USA.
Whitney S HenryDepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA; Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA, USA; Howard Hughes Medical Institute, Cambridge, MA, USA. Electronic address: wshenry@mit.edu.
Ankur JainWhitehead Institute for Biomedical Research, Cambridge, MA, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: ajain@wi.mit.edu.

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Jacqueline A. Lees · 1985 to 2026
$93.9M
TOXICOLOGY CORE UNITP30ES002109 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI NILES, JACQUIN C · 1985 to 2020
$25.6M
Pre-doctoral Training in Fundamental Approaches to Biochemistry and Cell and Molecular BiologyT32GM136540 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Mary Gehring, Michael Laub · 2021 to 2026
$9.5M
Elucidating the molecular and cellular functions of polyaminesR35GM151111 · NIGMS · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI Ankur Jain · 2023 to 2026
$1.9M
From humans and eukaryotes to viruses and pathogens; how transition metals shape catalysis and allosteryR35GM156452 · NIGMS · BRANDEIS UNIVERSITY · PI Maria-Eirini Pandelia · 2025 to 2026
$935k
NCI NIH HHS P30 CA014051NIEHS NIH HHS P30 ES002109NIGMS NIH HHS R35 GM151111NIGMS NIH HHS R35 GM156452NIGMS NIH HHS T32 GM136540
6 · The paper itself

Abstract

Polyamines are essential and evolutionarily conserved metabolites present at millimolar concentrations in mammalian cells. Cells tightly regulate polyamine homeostasis through complex feedback mechanisms, yet the precise role necessitating this regulation remains unclear. Here, we show that polyamines contribute to endogenous buffering of redox-active iron, providing a molecular link between polyamine metabolism and ferroptosis. Using a genome-wide CRISPR screen, we identified a synthetic lethal dependency between polyamine depletion and the key ferroptosis suppressor, glutathione peroxidase 4 (GPX4). Mechanistically, we show that polyamine deficiency triggers a redistribution of cellular iron, increasing the labile iron pool and upregulating ferritin. To directly visualize this iron buffering in living cells, we developed a genetically encoded fluorescent reporter for redox-active iron. Live-cell analysis revealed a striking inverse correlation between intracellular polyamine levels and redox-active iron at single-cell resolution. These findings reposition polyamines as key regulators of iron homeostasis, with implications for ferroptosis-linked disease states and cellular redox balance.

Indexed as

FerroptosisIronPolyaminesAnimalsFerritinsHomeostasisHumansOxidation-ReductionPhospholipid Hydroperoxide Glutathione PeroxidaseFerritinsIronPhospholipid Hydroperoxide Glutathione PeroxidasePolyaminesferroptosisgenetically encoded iron sensorGPX4iron homeostasislabile iron poolpolyaminesredox-active ironspermidinespermine

Identifiers

PMID42600612
PMCPMC13527661

What OpenQuestion holds

Textmetadata
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.