New Understanding of ER Membrane Expansion

How lipid metabolism gets coordinated with membrane growth in response to environment has remained an unexplained phenomenon. A 2021 paper by Papagiannidis et al. in the EMBO Journal explains key components in how cells manage this response.

Organelle biogenesis typically requires synthesis of new membrane and thus depends on lipid metabolism. A genetic screen identifies the ER protein Ice2p as a regulator of lipid metabolism and a major factor for ER membrane biogenesis, from Papagiannidis et al.

Papagiannidis et al. demonstrate a key regulatory step via the transmembrane protein Ice2p. Ice2p affects negative regulation of Pah1p (called lipin in metazoa) by inhibiting the Nem1-Spo7 phosphatase complex, which would normally activate Pah1p by dephosphorylation. The study shows that Ice2p also plays a role in transcriptional regulation of lipid synthesis genes, thereby providing a key pivot in the cellular need to make more membrane in response to ER stress.