Evidence map›Paper›PMID 34446561›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

Up-regulation of the manganese transporter SLC30A10 by hypoxia-inducible factors defines a homeostatic response to manganese toxicity.

Chunyi Liu, Thomas Jursa, Michael Aschner, Donald R Smith, Somshuvra Mukhopadhyay

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
4.1field-weighted citation impact, top 5% 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

35 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
  2. Review
  3. Overlaps in mammalian iron and manganese homeostasis: recent advances.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Elevated brain manganese induces motor disease by upregulating the kynurenine pathway of tryptophan metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  10. Article
  11. Metal Ion Signaling in Biomedicine.Chemical reviews · 2025
    Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. PHD2 enzyme is an intracellular manganese sensor that initiates the homeostatic response against elevated manganese.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  20. 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 3 institutions in 1 country.

Chunyi LiuDivision of Pharmacology & Toxicology, College of Pharmacy, Institute for Neuroscience, The University of Texas at Austin, Austin, TX 78712.
Thomas JursaDepartment of Microbiology and Environmental Toxicology, University of California, Santa Cruz, CA 95064.ORCID 0000-0002-7264-904X
Michael AschnerDepartment of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461.ORCID 0000-0002-2619-1656
Donald R SmithDepartment of Microbiology and Environmental Toxicology, University of California, Santa Cruz, CA 95064.
Somshuvra MukhopadhyayDivision of Pharmacology & Toxicology, College of Pharmacy, Institute for Neuroscience, The University of Texas at Austin, Austin, TX 78712; som@austin.utexas.edu.
The University of Texas at Austin · USUniversity of California, Santa Cruz · USAlbert Einstein College of Medicine · US

Funding

Regulation of manganese homeostasis and detoxification by SLC30A10R01ES024812 · NIEHS · UNIVERSITY OF TEXAS AT AUSTIN · PI Somshuvra Mukhopadhyay · 2016 to 2026
$5.7M
Role and mechanisms of excretion in manganese neurotoxicityR01ES031574 · NIEHS · UNIVERSITY OF TEXAS AT AUSTIN · PI MUKHOPADHYAY, SOMSHUVRA · 2020 to 2025
$3.5M
NIEHS NIH HHS R01 ES024812NIEHS NIH HHS R01 ES031574
6 · The paper itself

Abstract

Manganese (Mn) is an essential metal that induces incurable parkinsonism at elevated levels. However, unlike other essential metals, mechanisms that regulate mammalian Mn homeostasis are poorly understood, which has limited therapeutic development. Here, we discovered that the exposure of mice to a translationally relevant oral Mn regimen up-regulated expression of SLC30A10, a critical Mn efflux transporter, in the liver and intestines. Mechanistic studies in cell culture, including primary human hepatocytes, revealed that 1) elevated Mn transcriptionally up-regulated SLC30A10, 2) a hypoxia response element in the

Indexed as

HomeostasisAnimalsCation Transport ProteinsGlycineHep G2 CellsHumansHypoxiaHypoxia-Inducible Factor 1, alpha SubunitIsoquinolinesLiverManganeseMiceMice, Inbred C57BLMutationNeurotoxicity SyndromesCation Transport ProteinsGlycineHif1a protein, mouseHypoxia-Inducible Factor 1, alpha SubunitIsoquinolinesManganeseroxadustatSLC30A10 protein, humanHIFhomeostasismetalparkinsonismZnT10

Identifiers

PMID34446561
PMCPMC8536340
OpenAlexW3195216273

What OpenQuestion holds

Textmetadata
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.