ArticleCell death & disease2024
PGC-1α repression dysregulates lipid metabolism and induces lipid droplet accumulation in retinal pigment epithelium.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The Impact of a High-Fat Diet on Eye Health.Nutrients · 2025Pooled it
- Myeloid deficiency of RORα exacerbates lipid dysregulation and laser-induced choroidal neovascularization.Angiogenesis · 2026Article
- PGC-1α and PPARs cooperatively mediate photoreceptor neuroprotection in rd1 mouse inherited retinal degeneration.Cell death & disease · 2026Article
- Research Progress on the Pathogenesis and Diagnostic and Therapeutic Potential of Ciliopathies Regulated by IFT172.Clinical genetics · 2026Review
- Baicalin Protects ARPE-19 Cells Against BRVO-Related Hypoxic Injury by Preserving Mitochondrial Function and Inhibiting Ferroptosis.Antioxidants (Basel, Switzerland) · 2026Article
- Gut microbiota-derived taurolithocholic acid modulates myofiber-type switching via p38 MAPK/PGC-1α signaling underlying breed differences between Arbor Acres and Taoyuan chickens.Poultry science · 2026Article
- Photoreceptor Vulnerability to Ferroptosis: Membrane Phospholipid Peroxidation, Mitochondrial Homeostasis, and RPE-Photoreceptor Coupling.Current issues in molecular biology · 2026Review
- 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 · 2026Review
- 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
- Spontaneous whole retinal degeneration in aged Beclin1 heterozygous mice.Journal of neural transmission (Vienna, Austria : 1996) · 2026Article
- The roles of glycerophospholipids in the aging retina and age-related macular degeneration.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Review
- Mitochondrial-targeted therapy for osteoarthritis: Challenges and opportunities from basic research to clinical translation.Frontiers in immunology · 2026Review
- Thyroid Hormone Receptor β1 and PGC1α Coordinately Regulate OPA1/MFN2-Mediated Mitochondrial Fusion and UCP1-Mediated Lipid Browning in ccRCC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- HFrontiers in cell and developmental biology · 2026Review
- Integrative Landscape of Dry AMD Pathogenesis, Models, and Emerging Therapeutic Strategies.International journal of molecular sciences · 2025Review
- The intersection of mitochondria, lipids, and ferroptosis: a new avenue for dry age-related macular degeneration.Apoptosis : an international journal on programmed cell death · 2025Review
- Article
- Divergent Regulation of Mammary Lipogenesis byAnimals : an open access journal from MDPI · 2025Article
- Sleep-dependent clearance of brain lipids by peripheral blood cells.bioRxiv : the preprint server for biology · 2025Article
- Dysregulated serum lipid profiles in neovascular age-related macular degeneration revealed by UPLC‒MS/MS lipidomics.Lipids in health and disease · 2025Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Drusen, the yellow deposits under the retina, are composed of lipids and proteins, and represent a hallmark of age-related macular degeneration (AMD). Lipid droplets are also reported in the retinal pigment epithelium (RPE) from AMD donor eyes. However, the mechanisms underlying these disease phenotypes remain elusive. Previously, we showed that Pgc-1α repression, combined with a high-fat diet (HFD), induce drastic AMD-like phenotypes in mice. We also reported increased PGC-1α acetylation and subsequent deactivation in the RPE derived from AMD donor eyes. Here, through a series of in vivo and in vitro experiments, we sought to investigate the molecular mechanisms by which PGC-1α repression could influence RPE and retinal function. We show that PGC-1α plays an important role in RPE and retinal lipid metabolism and function. In mice, repression of Pgc-1α alone induced RPE and retinal degeneration and drusen-like deposits. In vitro inhibition of PGC1A by CRISPR-Cas9 gene editing in human RPE (ARPE19- PGC1A KO) affected the expression of genes responsible for lipid metabolism, fatty acid β-oxidation (FAO), fatty acid transport, low-density lipoprotein (LDL) uptake, cholesterol esterification, cholesterol biosynthesis, and cholesterol efflux. Moreover, inhibition of PGC1A in RPE cells caused lipid droplet accumulation and lipid peroxidation. ARPE19-PGC1A KO cells also showed reduced mitochondrial biosynthesis, impaired mitochondrial dynamics and activity, reduced antioxidant enzymes, decreased mitochondrial membrane potential, loss of cardiolipin, and increased susceptibility to oxidative stress. Our data demonstrate the crucial role of PGC-1α in regulating lipid metabolism. They provide new insights into the mechanisms involved in lipid and drusen accumulation in the RPE and retina during aging and AMD, which may pave the way for developing novel therapeutic strategies targeting PGC-1α.
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Registered trials
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