Phosphatidylinositol 3,4-bisphosphate-mediated exit from cell division counteracts early senescence and cataract formation

Cytokinetic membrane abscission is a spatially and temporally regulated process that requires the ESCRT-dependent control of membrane remodeling at the midbody, a subcellular organelle defining the cleavage site. Alteration of ESCRT function can lead to cataract, but the underlying mechanism and its relation to cytokinesis are unclear. Here, we define a lens-specific cytokinetic process that requires PI3K-C2α, its lipid product PI(3,4)P2, and the PI(3,4)P2-binding ESCRT-II subunit VPS36. We show that loss of each of these components leads to cytokinetic failure, thereby triggering premature senescence in the lens of fish, mice, and humans. Our results thus identify an evolutionarily conserved pathway for the cell-specific control of cytokinesis that serves to prevent early onset cataract by protecting from senescence. Website: https://www.dmbhs.unito.it/do/home.pl/View?doc=Hirsch_group.html

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