Evidence map›Paper›PMID 34623384›Full record

ArticleThe Journal of cell biology2021

PINK1 drives production of mtDNA-containing extracellular vesicles to promote invasiveness.

Nicolas Rabas, Sarah Palmer, Louise Mitchell, Shehab Ismail, Andrea Gohlke, Joel S Riley, Stephen W G Tait, Payam Gammage, Leandro Lemgruber Soares, Iain R Macpherson and 1 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed, 1 pooled it
8.0field-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

90 citing papers in PubMed, 1 synthesis or guideline pooled it, 134 citations in OpenAlex.

  1. Pooled it
  2. Review
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  10. Rab27: Molecular switch of tumor exosome secretion (Review).International journal of molecular medicine · 2026
    Review
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  12. Article
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  15. Article
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  18. Therapeutic and diagnostic potential of extracellular vesicle (EV)-mediated intercellular transfer of mitochondria and mitochondrial components.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Review
  19. Review
  20. Article

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

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Nicolas RabasBeatson Institute for Cancer Research, Glasgow, UK.
Sarah PalmerBeatson Institute for Cancer Research, Glasgow, UK.ORCID 0000-0002-7541-406X
Louise MitchellBeatson Institute for Cancer Research, Glasgow, UK.
Shehab IsmailBeatson Institute for Cancer Research, Glasgow, UK.ORCID 0000-0002-4150-1077
Andrea GohlkeBeatson Institute for Cancer Research, Glasgow, UK.ORCID 0000-0002-5447-5453
Joel S RileyBeatson Institute for Cancer Research, Glasgow, UK.ORCID 0000-0001-9170-5716
Stephen W G TaitBeatson Institute for Cancer Research, Glasgow, UK.ORCID 0000-0001-7697-132X
Payam GammageBeatson Institute for Cancer Research, Glasgow, UK.ORCID 0000-0003-1968-1726
Leandro Lemgruber SoaresGlasgow Imaging Facility, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.ORCID 0000-0003-2832-6806
Iain R MacphersonBeatson Institute for Cancer Research, Glasgow, UK.
Jim C NormanBeatson Institute for Cancer Research, Glasgow, UK.ORCID 0000-0002-0098-3014
Cancer Research UK Scotland Institute · GBUniversity of Glasgow · GB

Funding

Breast Cancer NowCancer Research UK 18277Cancer Research UK 20145Cancer Research UK 28291Cancer Research UK C596/A17196Cancer Research UK C596/A18076Medical Research Council MR/P01058X/1
6 · The paper itself

Abstract

The cystine-glutamate antiporter, xCT, supports a glutathione synthesis program enabling cancer cells to cope with metabolically stressful microenvironments. Up-regulated xCT, in combination with glutaminolysis, leads to increased extracellular glutamate, which promotes invasive behavior by activating metabotropic glutamate receptor 3 (mGluR3). Here we show that activation of mGluR3 in breast cancer cells activates Rab27-dependent release of extracellular vesicles (EVs), which can transfer invasive characteristics to "recipient" tumor cells. These EVs contain mitochondrial DNA (mtDNA), which is packaged via a PINK1-dependent mechanism. We highlight mtDNA as a key EV cargo necessary and sufficient for intercellular transfer of invasive behavior by activating Toll-like receptor 9 in recipient cells, and this involves increased endosomal trafficking of pro-invasive receptors. We propose that an EV-mediated mechanism, through which altered cellular metabolism in one cell influences endosomal trafficking in other cells, is key to generation and dissemination of pro-invasive microenvironments during mammary carcinoma progression.

Indexed as

Cell Line, TumorCisplatinDNA, MitochondrialDNA PackagingEndosomesExtracellular VesiclesHumansMitochondriaMitochondrial ProteinsNeoplasm InvasivenessProtein KinasesPTEN-Induced Putative Kinaserab27 GTP-Binding ProteinsReceptors, Metabotropic GlutamateTetraspanin 30Toll-Like Receptor 9CisplatinDNA, Mitochondrialmetabotropic glutamate receptor 3Mitochondrial ProteinsProtein KinasesPTEN-Induced Putative Kinaserab27 GTP-Binding ProteinsReceptors, Metabotropic GlutamateTetraspanin 30Toll-Like Receptor 9

Identifiers

PMID34623384
PMCPMC8641410
OpenAlexW3204068085

What OpenQuestion holds

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LicenceCC BY
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.