Evidence map›Paper›PMID 28296633›Full record

ArticleeLife2017

The vacuolar-ATPase complex and assembly factors, TMEM199 and CCDC115, control HIF1α prolyl hydroxylation by regulating cellular iron levels.

Anna L Miles, Stephen P Burr, Guinevere L Grice, James A Nathan

Open access · goldAbstract read
In one paragraph

Article in eLife, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 1 pooled it
4.5field-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

65 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Co-option of Lysosomal Machinery for Sponge Biosilicification.bioRxiv : the preprint server for biology · 2026
    Article
  5. Article
  6. Article
  7. Tacrolimus inhibits CVB3-targeted regulation of TFEB by PPP3/calcineurin.Frontiers in cellular and infection microbiology · 2026
    Article
  8. Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Mechanisms controlling cellular and systemic iron homeostasis.Nature reviews. Molecular cell biology · 2024
    Review
  17. Article
  18. Article
  19. Article
  20. Article

5 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

4 authors at 1 institution in 1 country.

Anna L MilesDepartment of Medicine, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
Stephen P BurrDepartment of Medicine, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
Guinevere L GriceDepartment of Medicine, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
James A NathanDepartment of Medicine, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.ORCID 0000-0002-0248-1632
University of Cambridge · GB

Funding

Medical Research Council MR/K50127X/1Wellcome TrustWellcome Trust 102770/Z/13/Z
6 · The paper itself

Abstract

Hypoxia Inducible transcription Factors (HIFs) are principally regulated by the 2-oxoglutarate and Iron(II) prolyl hydroxylase (PHD) enzymes, which hydroxylate the HIFα subunit, facilitating its proteasome-mediated degradation. Observations that HIFα hydroxylation can be impaired even when oxygen is sufficient emphasise the importance of understanding the complex nature of PHD regulation. Here, we use an unbiased genome-wide genetic screen in near-haploid human cells to uncover cellular processes that regulate HIF1α. We identify that genetic disruption of the Vacuolar H+ ATPase (V-ATPase), the key proton pump for endo-lysosomal acidification, and two previously uncharacterised V-ATPase assembly factors, TMEM199 and CCDC115, stabilise HIF1α in aerobic conditions. Rather than preventing the lysosomal degradation of HIF1α, disrupting the V-ATPase results in intracellular iron depletion, thereby impairing PHD activity and leading to HIF activation. Iron supplementation directly restores PHD catalytic activity following V-ATPase inhibition, revealing important links between the V-ATPase, iron metabolism and HIFs.

Indexed as

Protein Processing, Post-TranslationalAerobiosisHumansHydroxylationHypoxia-Inducible Factor 1, alpha SubunitIronMembrane ProteinsNerve Tissue ProteinsProlyl HydroxylasesVacuolar Proton-Translocating ATPasesVacuolesCcdc115 protein, humanHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitIronMembrane ProteinsNerve Tissue ProteinsProlyl HydroxylasesTMEM199 protein, humanVacuolar Proton-Translocating ATPasesbiochemistryCCDC115cell biologyferritinophagyHIFhumanHypoxia Inducible factorsIronPHDprolyl hydroxylationTMEM199transferrinVacuolar ATPasevATPaseVma12Vma22

Identifiers

PMID28296633
PMCPMC5391204
OpenAlexW2597215499

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.