ArticleAutophagy2023
Mitophagy initiates retrograde mitochondrial-nuclear signaling to guide retinal pigment cell heterogeneity.
Article in Autophagy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Retinal Pigment Epithelium Phagocytosis and Retinal Degenerative Diseases.Aging and disease · 2025Pooled it
- Angiotensin II and cAMP signaling pathways regulate mitochondrial biogenesis and activity in human adrenocortical cells.Journal of the Endocrine Society · 2026Article
- Article
- FASN mediates crosstalk between autophagy and lipid metabolism via the AMPK-MTOR pathway in early age-related macular degeneration.Autophagy · 2026Article
- A peripheral subpopulation of retinal pigment epithelium resists oxidative damage through SERPINE3-mediated caspase-1 inhibition.The Journal of clinical investigation · 2026Article
- Mitochondrial Metabolic Biomarkers in Periodontitis: Discovery and Clinical Validation.International dental journal · 2026Article
- Bioactive Properties of Carotenoids in Ocular Diseases: Antioxidant, Anti-Inflammatory, and Neuroprotective Effects.Nutrients · 2026Review
- Humanin Mitigates Aβ-Induced Retinal Pigment Epithelium Injury via AMPK-Beclin1-Dependent Mitophagy.Aging cell · 2026Article
- Autophagy-epithelial-mesenchymal transition crosstalk in acute respiratory distress syndrome: Mechanistic insights and therapeutic perspectives (Review).Experimental and therapeutic medicine · 2026Review
- Calcium at the Helm: Mechanisms and Therapeutic Targets in the Retinal Neurovascular Unit.Biomolecules · 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
- STING activation induces polarized cytokine secretion of IFN-β and IL-17A promoting photoreceptor death and choroidal disruption in age-related macular degeneration.Cell death & disease · 2026Article
- Molecular underpinnings of induced degenerative heterogeneity in the retinal pigment epithelium.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Glucocorticoid-induced RPE injury in ARPE-19 cells: association with excessive autophagy and AMPK/mTOR signaling.International journal of ophthalmology · 2026Article
- Defective chaperone-mediated autophagy in the retinal pigment epithelium of age-related macular degeneration patients.EMBO molecular medicine · 2025Article
- Prominin-1 Regulates Retinal Pigment Epithelium Homeostasis: Transcriptomic Insights into Degenerative Mechanisms.International journal of molecular sciences · 2025Article
- Targeting TIMM23 to overcome osteosarcoma chemoresistance.Cell death & disease · 2025Article
- Optimization and Application of Seahorse Glycolytic Stress Test in Mouse Corneal Tissues: Revealing Metabolic Profiles in Injury Models.Investigative ophthalmology & visual science · 2025Article
- Intermittent fasting attenuates glial hyperactivation and photoreceptor degeneration in a NaIOCommunications biology · 2025Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Age-related macular degeneration (AMD), the leading cause of blindness among the elderly, is without treatment for early disease. Degenerative retinal pigment epithelial (RPE) cell heterogeneity is a well-recognized but understudied pathogenic factor. Due to the daily phagocytosis of photoreceptor outer segments, unique photo-oxidative stress, and high metabolism for maintaining vision, the RPE has robust macroautophagy/autophagy, and mitochondrial and antioxidant networks. However, the autophagy subtype, mitophagy, in the RPE and AMD is understudied. Here, we found decreased PINK1 (PTEN induced kinase 1) in perifoveal RPE of early AMD eyes. PINK1-deficient RPE have impaired mitophagy and mitochondrial function that triggers death-resistant epithelial-mesenchymal transition (EMT). This reprogramming is mediated by novel retrograde mitochondrial-nuclear signaling (RMNS) through superoxide, NFE2L2 (NFE2 like bZIP transcription factor 2), TXNRD1 (thioredoxin reductase 1), and phosphoinositide 3-kinase (PI3K)-AKT (AKT serine/threonine kinase) that induced canonical transcription factors ZEB1 (zinc finger E-box binding homeobox 1) and SNAI1 (Snail family transcriptional repressor 1) and an EMT transcriptome. NFE2L2 deficiency disrupted RMNS that paradoxically normalized morphology but decreased function and viability. Thus, RPE heterogeneity is defined by the interaction of two cytoprotective pathways that is triggered by mitophagy function. By neutralizing the consequences of impaired mitophagy, an antioxidant dendrimer tropic for the RPE and mitochondria, EMT (a recognized AMD alteration) was abrogated to offer potential therapy for early AMD, a stage without treatment.
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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 OpenQuestion graph.