KIF23 regulates cytoskeleton dynamics for cytokinesis and mitochondrial function during oocyte meiosis

Cytoskeleton dynamics ensure multiple cellular progression during oocyte meiosis, which is critical for successful fertilization and early embryo development. KIF23, a member of the kinesin-6 superfamily, mediates intracellular transport and cell division in mammals, and server as a biomarker for cancer diagnosis and prognosis. In the present study, we explored the roles of KIF23 in mouse oocyte meiosis. Our results demonstrated that KIF23 depletion induces both polar body extrusion and asymmetry defects, and KIF23 is dispensable for meiotic spindle formation but interacts with NAT10 to modulate tubulin acetylation, thereby maintaining microtubule stability, kinetochore-microtubule attachment and preventing aneuploidy. Mass spectrometry data revealed that KIF23 associated with actin nucleators to regulate actin assembly, whose dysregulation underlies the defective asymmetric division in KIF23-deficient oocytes. Furthermore, KIF23 modulates anaphase spindle midzone and cleavage furrow formation by recruiting of PRC1, and governs contractile ring formation and constriction via the CDC42-p-MLC2. We also identified that KIF23 maintains p-DRP1-mediated mitochondrial homeostasis in an actin-dependent manner during oocyte meiosis. Collectively, our results establish KIF23 as a central molecular scaffold that integrates cytoskeleton dynamics-dependent cytokinesis and mitochondrial homeostasis in mouse oocyte meiosis.