Mitotic regulation of SREBP and ATF6 by separation of the Golgi and ER

The highly organized structure of the Golgi apparatus becomes compromised during mitosis. The Golgi cisternae unstack and form vesicles, which are then partitioned into the daughter cells. Here, we analyzed the fate of the SREBP and ATF6, two key transcription factors of sterol biogenesis and the unfolded protein response, respectively. During interphase the precursors of both transcription factors are silent in the ER, but upon activation signals SREBP and ATF6 move to the Golgi where they are activated by proteolytic cleavage by S1P and S2P. Since the spatial separation between the ER and the Golgi is the basis for the regulated activation, we investigated whether mitosis is sufficient to trigger activation. We found that the strict compartmentalization of the ER and the Golgi is maintained during mitosis to inhibit the activation of SREBP and ATF6.