Evidence map›Paper›PMID 33104284›Full record

ArticleCellular microbiology2021

Using genetically encoded heme sensors to probe the mechanisms of heme uptake and homeostasis in Candida albicans.

Ziva Weissman, Mariel Pinsky, Rebecca K Donegan, Amit R Reddi, Daniel Kornitzer

Open access · greenAbstract read
In one paragraph

Article in Cellular microbiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.7field-weighted citation impact, top 12% 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

17 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Siderophores and secondary metabolites produced byMicrobiology (Reading, England) · 2025
    Article
  6. Heme alters biofilm formation inMicrobiology spectrum · 2025
    Article
  7. Article
  8. Fluorometric Methods to Measure Bioavailable and Total Heme.Methods in molecular biology (Clifton, N.J.) · 2024
    Article
  9. Article
  10. Heme sensing and trafficking in fungi.Fungal biology reviews · 2023
    Article
  11. Article
  12. Article
  13. Article
  14. Heme Oxygenase-1 (Journal of fungi (Basel, Switzerland) · 2022
    Article
  15. Iron homeostasis and organismal aging.Ageing research reviews · 2021
    Review
  16. Article
  17. Molecular Epidemiology, Antifungal Susceptibility, and Virulence Evaluation ofFrontiers in cellular and infection microbiology · 2021
    Article
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

5 authors at 2 institutions in 2 countries.

Ziva WeissmanDepartment of Molecular Microbiology, B. Rappaport Faculty of Medicine, Technion-I.I.T., Haifa, Israel.
Mariel PinskyDepartment of Molecular Microbiology, B. Rappaport Faculty of Medicine, Technion-I.I.T., Haifa, Israel.
Rebecca K DoneganSchool of Chemistry and Biochemistry and Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, Georgia, USA.
Amit R ReddiSchool of Chemistry and Biochemistry and Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, Georgia, USA.
Daniel KornitzerDepartment of Molecular Microbiology, B. Rappaport Faculty of Medicine, Technion-I.I.T., Haifa, Israel.ORCID 0000-0002-5062-2735
Technion – Israel Institute of Technology · ILGeorgia Institute of Technology · US

Funding

Imaging heme based mitochondrial-cell signaling networks in cell and animal modelR33ES025661 · NIEHS · GEORGIA INSTITUTE OF TECHNOLOGY · PI REDDI, AMIT RAM · 2017 to 2019
$1.7M
Imaging heme based mitochondrial-cell signaling networks in cell and animal models of heavy metal toxicityR21ES025661 · NIEHS · GEORGIA INSTITUTE OF TECHNOLOGY · PI REDDI, AMIT RAM · 2015 to 2016
$416k
NIEHS NIH HHS R21 ES025661NIEHS NIH HHS R33 ES025661
6 · The paper itself

Abstract

Candida albicans is a major fungal pathogen that can utilise hemin and haemoglobin as iron sources in the iron-scarce host environment. While C. albicans is a heme prototroph, we show here that it can also efficiently utilise external heme as a cellular heme source. Using genetically encoded ratiometric fluorescent heme sensors, we show that heme extracted from haemoglobin and free hemin enter the cells with different kinetics. Heme supplied as haemoglobin is taken up via the Common in Fungal Extracellular Membrane (CFEM) hemophore cascade, and reaches the cytoplasm over several hours, whereas entry of free hemin via CFEM-dependent and independent pathways is much faster, less than an hour. To prevent an influx of extracellular heme from reaching toxic levels in the cytoplasm, the cells deploy Hmx1, a heme oxygenase. Hmx1 was previously suggested to be involved in utilisation of haemoglobin and hemin as iron sources, but we find that it is primarily required to prevent heme toxicity. Taken together, the combination of novel heme sensors with genetic analysis revealed new details of the fungal mechanisms of heme import and homeostasis, necessary to balance the uses of heme as essential cofactor and potential iron source against its toxicity.

Indexed as

HomeostasisBiosensing TechniquesCandida albicansCandidiasisFungal ProteinsHemeHeme Oxygenase (Decyclizing)HeminHemoglobinsHumansIronLuminescent ProteinsRecombinant Fusion ProteinsFungal ProteinsHemeHeme Oxygenase (Decyclizing)HeminHemoglobinsIronLuminescent ProteinsRecombinant Fusion Proteins

Identifiers

PMID33104284
PMCPMC7855654
OpenAlexW3094284950

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.