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Autophagy Requirements for Eye Lens Differentiation and Transparency

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Suppression of PI3K signaling is linked to autophagy activation and the spatiotemporal induction of the lens organelle free zone

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Summary: The terminal steps of lens cell differentiation require the elimination of all organelles to form a central Organelle Free Zone (OFZ) necessary for lens function. Blocking PI3K signaling leads to premature induction of autophagy within 24 hours, increasing LAMP1+ lysosomes and removing lens organelles from the center. Inhibiting the PI3K/Akt pathway alone can eliminate mitochondria and ER, while blocking all PI3K downstream signaling removes all organelles, including nuclei. The endogenous inhibitor PIK3IP1 associates with multiple PI3K p110 isoforms before OFZ formation, providing a possible mechanism for blocking PI3K signaling and activating autophagy during lens development.

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Rapamycin relieves the cataract caused by ablation of Gja8b through stimulating autophagy in zebrafish

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Transmembrane phospholipid translocation mediated by Atg9 is involved in autophagosome formation

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TDRD7 participates in lens development and spermiogenesis by mediating autophagosome maturation

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