ArticleJCI insight2021
Mitochondria-dependent phase separation of disease-relevant proteins drives pathological features of age-related macular degeneration.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
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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.
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Who cites it
41 citing papers in PubMed, 52 citations in OpenAlex.
- Lipid-driven membrane remodeling engages a lysosome-dependent adaptive repair program during retinal aging.Molecular neurodegeneration · 2026Article
- Neuronal death and accumulation of lipid droplets and glycogen granules within retinal pigment epithelium under the influence of mTOR and autophagy.Journal of neural transmission (Vienna, Austria : 1996) · 2026Article
- From Genetic Diagnosis to Therapeutic Implementation in Retinal Diseases: Translational Advances and Persistent Bottlenecks.Biomedicines · 2026Review
- Age-related macular degeneration and cerebral amyloid angiopathy have similar pathologies from cholesterol-APOE-amyloid-β-complement mediated inflammation.Progress in retinal and eye research · 2026Review
- Acid sphingomyelinase inhibition restores RPE homeostasis and photoreceptor function in preclinical Stargardt macular degeneration models.bioRxiv : the preprint server for biology · 2026Article
- A phase separation hypothesis for the biological function of PrP: the role of multivalent interactions at the plasma membrane.Biochemical Society transactions · 2026Review
- Age-Driven Lipid Remodeling Activates Lysosome-Mediated Plasma Membrane Repair.Research square · 2026Article
- Retinal pigment epithelium pathology in age-related macular degeneration: mitigation with melatonin.Frontiers in medicine · 2026Review
- Nrf2 Activated by PD-MSCs Attenuates Oxidative Stress in a Hydrogen Peroxide-Injured Retinal Pigment Epithelial Cell Line.Antioxidants (Basel, Switzerland) · 2025Article
- Redox regulation of LSD1/CATALASE 2 phase separation condensates controls location and functions.The New phytologist · 2025Article
- Review
- Molecular Determinants of the Human Retinal Pigment Epithelium Cell Fate and Potential Pharmacogenomic Targets for Precision Medicine.International journal of molecular sciences · 2025Article
- Retinal Autophagy for Sustaining Retinal Integrity as a Proof of Concept for Age-Related Macular Degeneration.International journal of molecular sciences · 2025Review
- Phase separation in mitochondrial fate and mitochondrial diseases.Proceedings of the National Academy of Sciences of the United States of America · 2025Review
- Gene therapy for age-related macular degeneration: a promising frontier in vision preservation.Cell communication and signaling : CCS · 2025Review
- Artemisinin and Its Derivatives: Promising Therapeutic Agents for Age-Related Macular Degeneration.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Suppressing APOE4-induced neural pathologies by targeting the VHL-HIF axis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- How crosstalk between mitochondria, lysosomes, and other organelles can prevent or promote dry age-related macular degeneration.Experimental eye research · 2025Review
- Article
- Potential Role of NUR77 in the Aging Retinal Pigment Epithelium and Age-Related Macular Degeneration.Advances in experimental medicine and biology · 2025Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Age-related macular degeneration (AMD) damages the retinal pigment epithelium (RPE), the tissue that safeguards photoreceptor health, leading to irreversible vision loss. Polymorphisms in cholesterol and complement genes are implicated in AMD, yet mechanisms linking risk variants to RPE injury remain unclear. We sought to determine how allelic variants in the apolipoprotein E cholesterol transporter modulate RPE homeostasis and function. Using live-cell imaging, we show that inefficient cholesterol transport by the AMD risk-associated ApoE2 increases RPE ceramide, leading to autophagic defects and complement-mediated mitochondrial damage. Mitochondrial injury drives redox state-sensitive cysteine-mediated phase separation of ApoE2, forming biomolecular condensates that could nucleate drusen. The protective ApoE4 isoform lacks these cysteines and is resistant to phase separation and condensate formation. In Abca-/- Stargardt macular degeneration mice, mitochondrial dysfunction induces liquid-liquid phase separation of p62/SQSTM1, a multifunctional protein that regulates autophagy. Drugs that decrease RPE cholesterol or ceramide prevent mitochondrial injury and phase separation in vitro and in vivo. In AMD donor RPE, mitochondrial fragmentation correlates with ApoE and p62 condensates. Our studies demonstrate that major AMD genetic and biological risk pathways converge upon RPE mitochondria, and identify mitochondrial stress-mediated protein phase separation as an important pathogenic mechanism and promising therapeutic target in AMD.
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Registered trials
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 Socratic graph.