Evidence map›Paper›PMID 40631118›Full record

ArticlebioRxiv : the preprint server for biology2025

Polyamines buffer labile iron to suppress ferroptosis.

Pushkal Sharma, Heather R Keys, Sebastian Müller, Ivan S Pires, Ryan Mansell, Shinya Imada, Tenzin Kunchok, Millenia Waite, Christalyn Ausler, Bingbing Yuan and 5 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Pushkal SharmaWhitehead Institute for Biomedical Research, Cambridge, MA, USA.
Heather R KeysWhitehead Institute for Biomedical Research, Cambridge, MA, USA.
Sebastian MüllerInstitut Curie, CNRS, INSERM, PSL Research University, Paris, France.
Ivan S PiresDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Ryan MansellKoch Institute for Integrative Cancer Research at MIT, Cambridge, MA, USA.
Shinya ImadaKoch 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.
Christalyn AuslerWhitehead 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.
Paula T HammondDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Raphaël RodriguezInstitut Curie, CNRS, INSERM, PSL Research University, Paris, France.
Whitney HenryKoch Institute for Integrative Cancer Research at MIT, Cambridge, MA, USA.
Ankur JainWhitehead Institute for Biomedical Research, Cambridge, MA, USA.

Funding

Elucidating the molecular and cellular functions of polyaminesR35GM151111 · NIGMS · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI Ankur Jain · 2023 to 2026
$1.9M
NIGMS NIH HHS R35 GM151111
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 function as endogenous buffers of redox-active iron, providing a molecular link between polyamine metabolism and ferroptosis. Using genome-wide CRISPR screens, we identified a synthetic lethal dependency between polyamine depletion and the key ferroptosis suppressor, 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.

Identifiers

PMID40631118
PMCPMC12236739

What OpenQuestion holds

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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.