ArticleExperimental cell research2022
Suppression of PI3K signaling is linked to autophagy activation and the spatiotemporal induction of the lens organelle free zone.
Article in Experimental cell research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- The role of autophagy in ocular health: mechanisms, pathologies, and therapeutic strategies.Biology direct · 2026Pooled it
- Coumarins as modulators of autophagy and PI3K/mTOR signaling: implications for next-generation cancer therapies.Biomedical journal · 2026Review
- Autophagy in ocular diseases: from mechanisms to therapeutic potential.Frontiers in cell and developmental biology · 2026Review
- The 3D Genome Structure of a Blcap-Linked Silencer Loop Regulates Terminal Differentiation During Lens Fiber Cell Denucleation.Investigative ophthalmology & visual science · 2025Article
- Exploiting autophagy and related pathways: pioneering new horizons in cataract therapy.Apoptosis : an international journal on programmed cell death · 2025Review
- The link of FOXO1 and FOXO4 transcription factors to development of the lens.Developmental dynamics : an official publication of the American Association of Anatomists · 2025Article
- A bibliometric and visualized analysis of the pathogenesis of cataracts from 1999 to 2023.Heliyon · 2024Article
- Multiomic analysis implicates FOXO4 in genetic regulation of chick lens fiber cell differentiation.Developmental biology · 2023Article
- The involvement of caspases in the process of nuclear removal during lens fiber cell differentiation.Cell death discovery · 2023Article
- HSF4 Transcriptionally Activates Autophagy by Regulating ATG9a During Lens Terminal Differentiation.Investigative ophthalmology & visual science · 2023Article
- Review
- Repurposing a Cyclin-Dependent Kinase 1 (CDK1) Mitotic Regulatory Network to Complete Terminal Differentiation in Lens Fiber Cells.Investigative ophthalmology & visual science · 2023Article
- Impact of α-crystallin protein loss on zebrafish lens development.Experimental eye research · 2023Article
- AUTOPHAGY IN THE EYE: FROM PHYSIOLOGY TO PATHOPHYSOLOGY.Autophagy reports · 2023Article
- Article
- Review
- The Pro-Fibrotic Response to Lens Injury Is Signaled in a PI3K Isoform-Specific Manner.Biomolecules · 2022Article
- The link between inhibition of PI3K signaling, induction of autophagy, and elimination of organelles to form the lens organelle-free zone.Autophagy reports · 2022Article
- Methodologies to unlock the molecular expression and cellular structure of ocular lens epithelial cells.Frontiers in cell and developmental biology · 2022Article
- Differentially expressed gene profiles and associated ceRNA network in ATG7-Deficient lens epithelial cells under oxidative stress.Frontiers in genetics · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The terminal steps of lens cell differentiation require elimination of all organelles to create a central Organelle Free Zone (OFZ) that is required for lens function of focusing images on the retina. Previous studies show that the spatiotemporal elimination of these organelles during development is autophagy-dependent. We now show that the inhibition of PI3K signaling in lens organ culture results in the premature induction of autophagy within 24 h, including a significant increase in LAMP1+ lysosomes, and the removal of lens organelles from the center of the lens. Specific inhibition of just the PI3K/Akt signaling axis was directly linked to the elimination of mitochondria and ER, while pan-PI3K inhibitors that block all PI3K downstream signaling removed all organelles, including nuclei. Therefore, blocking the PI3K/Akt pathway was alone insufficient to remove nuclei. RNAseq analysis revealed increased mRNA levels of the endogenous inhibitor of PI3K activation, PIK3IP1, in differentiating lens fiber cells preceding the induction of OFZ formation. Co-immunoprecipitation confirmed that PIK3IP1 associates with multiple PI3K p110 isoforms just prior to formation of the OFZ, providing a likely endogenous mechanism for blocking all PI3K signaling and activating the autophagy pathway required to form the OFZ during lens development.
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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.