Evidence map›Paper›PMID 42723073›Full record

ArticleMolecular neurodegeneration2026

Lipid-driven membrane remodeling engages a lysosome-dependent adaptive repair program during retinal aging.

Emily Tom, Fangyuan Gao, Carolina N Franco, Adrian Wong, Nathan Kemmerer, Zichen Wang, Amit Jairaman, Qianlan Xu, Yinyin Zhuang, Samuel W Du and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular neurodegeneration, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

20 authors.

Emily TomDepartment of Physiology and Biophysics, School of Medicine, University of California, Irvine, Irvine, CA, USA.
Fangyuan GaoGavin Herbert Eye Institute - Brunson Center for Translational Vision Research, Department of Ophthalmology and Visual Sciences, University of California, Irvine, Irvine, CA, USA.
Carolina N FrancoDepartment of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University of California, Irvine, Irvine, CA, USA.
Adrian WongDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, USA.
Nathan KemmererShiley Eye Institute, University of California, San Diego, La Jolla, CA, USA.
Zichen WangDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, USA.
Amit JairamanDepartment of Physiology and Biophysics, School of Medicine, University of California, Irvine, Irvine, CA, USA.
Qianlan XuDepartment of Physiology and Biophysics, School of Medicine, University of California, Irvine, Irvine, CA, USA.
Yinyin ZhuangDepartment of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA.
Samuel W DuDepartment of Physiology and Biophysics, School of Medicine, University of California, Irvine, Irvine, CA, USA.
Grazyna PalczewskaGavin Herbert Eye Institute - Brunson Center for Translational Vision Research, Department of Ophthalmology and Visual Sciences, University of California, Irvine, Irvine, CA, USA.
Krzysztof PalczewskiDepartment of Physiology and Biophysics, School of Medicine, University of California, Irvine, Irvine, CA, USA.
Itay BudinDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, USA.
Shivashankar OthyDepartment of Physiology and Biophysics, School of Medicine, University of California, Irvine, Irvine, CA, USA.
Xiaoyu ShiDepartment of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA.
Vera L BonilhaDepartment of Ophthalmic Research, Cleveland Clinic, Cleveland, OH, USA.
Johannes SchoenebergDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, USA.
Karl J WahlinShiley Eye Institute, University of California, San Diego, La Jolla, CA, USA.
Lauren V AlbrechtDepartment of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University of California, Irvine, Irvine, CA, USA.
Dorota Skowronska-KrawczykDepartment of Physiology and Biophysics, School of Medicine, University of California, Irvine, Irvine, CA, USA. dorotask@hs.uci.edu.ORCID 0000-0002-5758-4225

Funding

STRUCTURAL STUDIES OF ARRESTINSR01EY009339 · NEI · UNIVERSITY OF WASHINGTON · PI KISER, PHILIP DAVID, PALCZEWSKI, KRZYSZTOF · 1992 to 2025
$16.0M
RESOURCE/SERVICE CORE C - MOLECULAR INFORMATICS MODULEP30EY025585 · NEI · CLEVELAND CLINIC LERNER COM-CWRU · PI BELA ANAND-APTE · 2016 to 2026
$7.7M
NEI UCI Center Core Grant for Vision ResearchP30EY034070 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Vladimir Jivkov Kefalov · 2022 to 2026
$3.7M
Tissue-Specific Mechanisms of Regulatory T Cells in the CNS during Autoimmune EncephalomyelitisR01AI168063 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI Shivashankar Othy · 2022 to 2026
$2.5M
Correlating Genomic AMD Risk Variants with Lipid Composition and Phagocytic Function of Patient-Derived Induced Pluripotent Stem Cell (iPSC)-derived Retinal Pigment Epithelium (RPE)U01EY034594 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI SKOWRONSKA-KRAWCZYK, DOROTA, WAHLIN, KARL J · 2022 to 2025
$1.6M
NEI NIH HHS P30 EY025585NEI NIH HHS P30 EY034070NEI NIH HHS R01 EY009339NEI NIH HHS U01 EY034594NIAID NIH HHS R01 AI168063NSF 2341058
6 · The paper itself

Abstract

Age-associated remodeling of membrane lipid composition has been implicated in cellular dysfunction, yet the mechanisms linking lipid changes to membrane integrity and disease remain poorly defined. In the retinal pigment epithelium (RPE), lipid dysregulation is strongly associated with aging and age-related macular degeneration (AMD), a neurodegenerative disease of the central nervous system, but the causal pathways remain unclear. Here, we identify reduced activity of the lipid elongase ELOVL2 as a central driver of age-dependent membrane remodeling. Loss of ELOVL2-dependent polyunsaturated fatty acid (PUFA) elongation shifts plasma membrane lipid composition, leading to altered membrane biophysical properties and compromised membrane integrity. In response to this stress, RPE cells do not undergo apoptosis but instead activate a lysosome-dependent plasma membrane repair program that preserves barrier function under metabolic challenge. However, this adaptive response drives spatially polarized lysosomal exocytosis, promoting extracellular remodeling and accumulation of sub-RPE deposits associated with aging and AMD. Restoration of ELOVL2-derived lipid products reverses membrane abnormalities and suppresses lysosome-mediated remodeling phenotypes, demonstrating direct metabolic control of membrane homeostasis. Together, these findings define an ELOVL2-dependent lipid-lysosome axis that links PUFA elongation to plasma membrane integrity and reveals how compensatory repair mechanisms can contribute to tissue remodeling and disease progression in aging epithelia.

Indexed as

AgingCell MembraneLysosomesMacular DegenerationMembrane LipidsRetinaRetinal Pigment EpitheliumAcetyltransferasesAnimalsFatty Acid ElongasesHumansMiceAcetyltransferasesFatty Acid ElongasesMembrane LipidsAge-related macular degeneration (AMD)AgingLysosomal exocytosisMembrane remodelingNeurodegeneration

Identifiers

PMID42723073
PMCPMC13563809

What OpenQuestion holds

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Registered trials

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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.