Evidence map›Paper›PMID 26287972›Full record

ArticlePloS one2015

Identification of the Mitochondrial Heme Metabolism Complex.

Amy E Medlock, Mesafint T Shiferaw, Jason R Marcero, Ajay A Vashisht, James A Wohlschlegel, John D Phillips, Harry A Dailey

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

83 citing papers in PubMed, 107 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. More than a ring: the emerging role of heme in angiogenesis.Cell communication and signaling : CCS · 2026
    Review
  6. Article
  7. Localized heme sensing through a ternary molecular glue.bioRxiv : the preprint server for biology · 2026
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. A reversible feedback mechanism regulating mitochondrial heme synthesis.bioRxiv : the preprint server for biology · 2025
    Article
  13. Mechanisms of heme transport in the mitochondria.Biochemical Society transactions · 2025
    Review
  14. Article
  15. Biogenesis of CytochromesACS infectious diseases · 2025
    Article
  16. Review
  17. Epigenetic control of tetrapyrrole biosynthesis by m4C DNA methylation in a cyanobacterium.DNA research : an international journal for rapid publication of reports on genes and genomes · 2024
    Article
  18. Biogenesis of cytochromesbioRxiv : the preprint server for biology · 2024
    Article
  19. Update on heme biosynthesis, tissue-specific regulation, heme transport, relation to iron metabolism and cellular energy.Liver international : official journal of the International Association for the Study of the Liver · 2024
    Review
  20. Key GenesGenes · 2024
    Article

23 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

7 authors at 3 institutions in 1 country.

Amy E MedlockBiomedical and Health Sciences Institute, University of Georgia, Athens, Georgia, United States of America; Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia, United States of America; GRU-UGA Medical Partnership, University of Georgia, Athens, Georgia, United States of America.
Mesafint T ShiferawBiomedical and Health Sciences Institute, University of Georgia, Athens, Georgia, United States of America; Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia, United States of America; GRU-UGA Medical Partnership, University of Georgia, Athens, Georgia, United States of America.
Jason R MarceroBiomedical and Health Sciences Institute, University of Georgia, Athens, Georgia, United States of America; Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia, United States of America.
Ajay A VashishtDepartment of Biological Chemistry and the Institute of Genomics and Proteomics, University of California Los Angeles, Los Angeles, California, United States of America.
James A WohlschlegelDepartment of Biological Chemistry and the Institute of Genomics and Proteomics, University of California Los Angeles, Los Angeles, California, United States of America.
John D PhillipsDivision of Hematology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.
Harry A DaileyBiomedical and Health Sciences Institute, University of Georgia, Athens, Georgia, United States of America; Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia, United States of America; Department of Microbiology, University of Georgia, Athens, Georgia, United States of America.
University of Georgia · USUniversity of California, Los Angeles · USUniversity of Utah · US

Funding

Porphyrias Consortium: SupplementU54DK083909 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI DESNICK, ROBERT J · 2009 to 2023
$18.5M
Proteolytic Control of Iron Metabolism by the Ubiquitin Ligase FBXL5R01GM089778 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WOHLSCHLEGEL, JAMES AKIRA · 2010 to 2023
$4.0M
PORPHYRIN BIOSYNTHESIS IN NORMAL AND DISEASE STATESR01DK020503 · NIDDK · UNIVERSITY OF UTAH · PI PARKER, CHARLES J, PHILLIPS, JOHN DEARBORN · 1986 to 2012
$3.3M
Erythroid heme synthesis regulation via the ferrochelatase [2Fe-2S] clusterR01DK096051 · NIDDK · UNIVERSITY OF GEORGIA · PI DAILEY, HARRY A · 2012 to 2015
$1.5M
PORPHYRIN BIOSYNTHESIS IN NORMAL AND DISEASE STATESR37DK020503 · NIDDK · UNIVERSITY OF UTAH · PI KUSHNER, JAMES P · 1993 to 2001
$463k
Porphyrin Biosynthesis in Normal and Disease StatesR56DK020503 · NIDDK · UNIVERSITY OF UTAH · PI PHILLIPS, JOHN DEARBORN · 2013 to 2013
$149k
NIDDK NIH HHS DK020503NIDDK NIH HHS DK083909NIDDK NIH HHS DK096051NIDDK NIH HHS R01 DK020503NIDDK NIH HHS R01 DK096051NIDDK NIH HHS R37 DK020503NIDDK NIH HHS R56 DK020503NIDDK NIH HHS U54 DK083909NIGMS NIH HHS GM089778NIGMS NIH HHS R01 GM089778
6 · The paper itself

Abstract

Heme is an essential cofactor for most organisms and all metazoans. While the individual enzymes involved in synthesis and utilization of heme are fairly well known, less is known about the intracellular trafficking of porphyrins and heme, or regulation of heme biosynthesis via protein complexes. To better understand this process we have undertaken a study of macromolecular assemblies associated with heme synthesis. Herein we have utilized mass spectrometry with coimmunoprecipitation of tagged enzymes of the heme biosynthetic pathway in a developing erythroid cell culture model to identify putative protein partners. The validity of these data obtained in the tagged protein system is confirmed by normal porphyrin/heme production by the engineered cells. Data obtained are consistent with the presence of a mitochondrial heme metabolism complex which minimally consists of ferrochelatase, protoporphyrinogen oxidase and aminolevulinic acid synthase-2. Additional proteins involved in iron and intermediary metabolism as well as mitochondrial transporters were identified as potential partners in this complex. The data are consistent with the known location of protein components and support a model of transient protein-protein interactions within a dynamic protein complex.

Indexed as

5-Aminolevulinate SynthetaseAnimalsATP-Binding Cassette TransportersCell Line, TumorFerrochelataseHemeHumansMiceMitochondriaMultiprotein ComplexesPorphyrinsProtoporphyrinogen Oxidase5-Aminolevulinate SynthetaseAbcb10 protein, mouseATP-Binding Cassette TransportersFerrochelataseHemeMultiprotein ComplexesPorphyrinsProtoporphyrinogen Oxidase

Identifiers

PMID26287972
PMCPMC4545792
OpenAlexW2258975283

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.