Evidence map›Paper›PMID 40082403›Full record

ArticleNature communications2025

PNPLA6 regulates retinal homeostasis by choline through phospholipid turnover.

Takashi Ono, Yoshitaka Taketomi, Takayoshi Higashi, Hiroyasu Sato, Chika Mochizuki-Ono, Yuki Nagasaki, Takashi Ueta, Takashi Miyai, Suzumi M Tokuoka, Yoshiya Oda and 9 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
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

10 citing papers in PubMed.

  1. Article
  2. International journal of molecular sciences · 2026
    Article
  3. Polyunsaturated fatty acid metabolism in the retinal pigment epithelium and its association with outer retinal disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. The cyclic nucleotide binding sites of Swiss-Cheese, thebioRxiv : the preprint server for biology · 2025
    Article
  9. Review
  10. Novel variant inFrontiers in genetics · 2025
    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

19 authors.

Takashi OnoLaboratory of Microenvironmental and Metabolic Health Science, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.ORCID http://orcid.org/0000-0002-1288-2798
Yoshitaka TaketomiLaboratory of Microenvironmental and Metabolic Health Science, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Takayoshi HigashiLaboratory of Microenvironmental and Metabolic Health Science, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.ORCID http://orcid.org/0000-0002-5262-091X
Hiroyasu SatoLaboratory of Microenvironmental and Metabolic Health Science, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Chika Mochizuki-OnoLaboratory of Microenvironmental and Metabolic Health Science, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Yuki NagasakiLaboratory of Microenvironmental and Metabolic Health Science, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.ORCID http://orcid.org/0000-0002-4717-6877
Takashi UetaDepartment of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.ORCID http://orcid.org/0000-0001-5995-7438
Takashi MiyaiDepartment of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Suzumi M TokuokaDepartment of Lipidomics, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Yoshiya OdaDepartment of Lipidomics, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Yasumasa NishitoCenter for Basic Technology Research, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo, Japan.
Tomio OnoCenter for Basic Technology Research, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo, Japan.
Choji TayaCenter for Basic Technology Research, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo, Japan.
Satoru ArataFaculty of Arts and Sciences at Fujiyoshida, Showa University, Fuji-yoshida-shi, Yamanashi, Japan.
Sumiko WatanabeDepartment of Retinal Biology and Pathology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Tomoyoshi SogaInstitute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan.ORCID http://orcid.org/0000-0001-9502-2509
Tetsuya HirabayashiBiomembrane group, Technology Research Division, Center for Basic Technology Research, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo, Japan.ORCID http://orcid.org/0000-0001-8099-5367
Makoto AiharaDepartment of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.ORCID http://orcid.org/0000-0001-6810-0583
Makoto MurakamiLaboratory of Microenvironmental and Metabolic Health Science, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan. makmurak@m.u-tokyo.ac.jp.ORCID http://orcid.org/0000-0002-4565-6017

Funding

Japan Agency for Medical Research and Development (AMED) JP24gm1210013MEXT | Japan Society for the Promotion of Science (JSPS) JP20H05691MEXT | Japan Society for the Promotion of Science (JSPS) JP20J12307MEXT | Japan Society for the Promotion of Science (JSPS) JP24K19806Takeda Science Foundation 2024044197
6 · The paper itself

Abstract

Although mutations in human patatin-like phospholipase PNPLA6 are associated with hereditary retinal degenerative diseases, its mechanistic action in the retina is poorly understood. Here, we uncover the molecular mechanism by which PNPLA6 dysfunction disturbs retinal homeostasis and visual function. PNPLA6, by acting as a phospholipase B, regulates choline mobilization from phosphatidylcholine and subsequent choline turnover for phosphatidylcholine regeneration in retinal pigment epithelial cells. PNPLA6-driven choline is supplied from retinal pigment epithelial cells to adjacent photoreceptor cells to support their survival. Inhibition of this pathway results in abnormal morphology, proliferation, metabolism, and functions of retinal pigment epithelial and photoreceptor cells, and mice with retina-specific PNPLA6 deletion exhibit retinitis pigmentosa-like retinal degeneration. Notably, these abnormalities are entirely rescued by choline supplementation. Thus, PNPLA6 plays an essential role in retinal homeostasis by controlling choline availability for phospholipid recycling and provide a framework for the development of an ophthalmic drug target for retinal degeneration.

Indexed as

CholinePhospholipasesPhospholipidsRetinaAnimalsHomeostasisHumansMiceMice, Inbred C57BLMice, KnockoutPhosphatidylcholinesPhotoreceptor Cells, VertebrateRetinal Pigment EpitheliumRetinitis PigmentosaCholinePhosphatidylcholinesPhospholipasesPhospholipids

Identifiers

PMID40082403
PMCPMC11906636

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.