Pericentrosomal Redistribution of the Endoplasmic Reticulum Ensures Organelle Symmetric Inheritance and Mitotic Progression

ABSTRACT Symmetric cell division entails the equal distribution of cellular components to daughter cells. However, the mechanisms governing organelle segregation remain elusive. The endoplasmic reticulum (ER), comprising perinuclear sheets and peripheral tubules in interphase, serves as a central hub for sensing cellular states and coordinating other organelle dynamics. Here, we show that upon mitotic entry, the ER undergoes reverse redistribution: tubular ER accumulates around the centrosomes, while sheet‐like ER relocates to the periphery. Mechanistically, the tubular ER protein Reticulon 4 (RTN4) is phosphorylated by cyclin‐dependent kinase 1 (CDK1) during early mitosis. Phosphorylation promotes the interaction between RTN4 and Rab11, leading to the dynein‐dependent enrichment of RTN4 around centrosomes and consequently driving the tubularization of the pericentrosomal ER. RTN4‐mediated mitotic ER reorganization ensures symmetric distribution and inheritance of the ER, further contributing to the symmetric segregation of other organelles and mitotic fidelity. Thus, our study uncovers the mechanism of ER symmetry remodeling during early mitosis and its roles in organelle inheritance and mitotic progression.