Evidence map›Paper›PMID 23189181›Full record

ArticlePloS one2012

Mitochondrial localization of ABC transporter ABCG2 and its function in 5-aminolevulinic acid-mediated protoporphyrin IX accumulation.

Hirotsugu Kobuchi, Koko Moriya, Tetsuya Ogino, Hirofumi Fujita, Keiji Inoue, Taro Shuin, Tatsuji Yasuda, Kozo Utsumi, Toshihiko Utsumi

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 1 pooled it
4.4field-weighted citation impact, top 4% 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

61 citing papers in PubMed, 1 synthesis or guideline pooled it, 136 citations in OpenAlex.

  1. 5-Aminolevulinic acid (5-ALA) in paediatric brain tumour surgery-a systematic review and exploration of fluorophore alternatives.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2025
    Pooled it
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Metabolism-guided development of Ko143 analogs as ABCG2 inhibitors.European journal of medicinal chemistry · 2023
    Article
  11. Review
  12. Review
  13. Attenuation of Dopaminergic Neurodegeneration in aJournal of developmental biology · 2023
    Article
  14. Review
  15. Modulating Glycolysis to Improve Cancer Therapy.International journal of molecular sciences · 2023
    Review
  16. Review
  17. The Role of ABC Transporters in Skin Cells Exposed to UV Radiation.International journal of molecular sciences · 2022
    Review
  18. Article
  19. Article
  20. Review

1 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

9 authors at 3 institutions in 1 country.

Hirotsugu KobuchiDepartment of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. hkobuchi@md.okayama-u.ac.jp
Koko Moriya
Tetsuya Ogino
Hirofumi Fujita
Keiji Inoue
Taro Shuin
Tatsuji Yasuda
Kozo Utsumi
Toshihiko Utsumi
Okayama University · JPYamaguchi University · JPOkayama Prefectural University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Accumulation of protoporphyrin IX (PpIX) in malignant cells is the basis of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy. We studied the expression of proteins that possibly affect ALA-mediated PpIX accumulation, namely oligopeptide transporter-1 and -2, ferrochelatase and ATP-binding cassette transporter G2 (ABCG2), in several tumor cell lines. Among these proteins, only ABCG2 correlated negatively with ALA-mediated PpIX accumulation. Both a subcellular fractionation study and confocal laser microscopic analysis revealed that ABCG2 was distributed not only in the plasma membrane but also intracellular organelles, including mitochondria. In addition, mitochondrial ABCG2 regulated the content of ALA-mediated PpIX in mitochondria, and Ko143, a specific inhibitor of ABCG2, enhanced mitochondrial PpIX accumulation. To clarify the possible roles of mitochondrial ABCG2, we characterized stably transfected-HEK (ST-HEK) cells overexpressing ABCG2. In these ST-HEK cells, functionally active ABCG2 was detected in mitochondria, and treatment with Ko143 increased ALA-mediated mitochondrial PpIX accumulation. Moreover, the mitochondria isolated from ST-HEK cells exported doxorubicin probably through ABCG2, because the export of doxorubicin was inhibited by Ko143. The susceptibility of ABCG2 distributed in mitochondria to proteinase K, endoglycosidase H and peptide-N-glycosidase F suggested that ABCG2 in mitochondrial fraction is modified by N-glycans and trafficked through the endoplasmic reticulum and Golgi apparatus and finally localizes within the mitochondria. Thus, it was found that ABCG2 distributed in mitochondria is a functional transporter and that the mitochondrial ABCG2 regulates ALA-mediated PpIX level through PpIX export from mitochondria to the cytosol.

Indexed as

AdenosineAminolevulinic AcidATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily G, Member 2Biological TransportCell Line, TumorDiketopiperazinesDoxorubicinEndoplasmic ReticulumFerrochelataseGene ExpressionGlycosylationGolgi ApparatusHEK293 CellsHeterocyclic Compounds, 4 or More RingsHumans3-(6-isobutyl-9-methoxy-1,4-dioxo-1,2,3,4,6,7,12,12a-octahydropyrazino(1',2'-1,6)pyrido(3,4-b)indol-3-yl)propionic acid tert-butyl esterABCG2 protein, humanAdenosineAminolevulinic AcidATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily G, Member 2DiketopiperazinesDoxorubicinFerrochelataseHeterocyclic Compounds, 4 or More Ringshydrogen-coupled oligopeptide transporter PepT2Neoplasm ProteinsPeptide Transporter 1protoporphyrin IXProtoporphyrinsRecombinant Fusion ProteinsSLC15A1 protein, humanSymporters

Identifiers

PMID23189181
PMCPMC3506543
OpenAlexW2161907161

What OpenQuestion holds

Textmetadata
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.