Orchestrating phospholipid biosynthesis: Phosphatidic acid conducts and Opi1p performs

Abstract

Phosphatidic acid (PA) and the conserved integral ER membrane protein Scs2p regulate localization of the transcriptional repressor Opi1p, which controls expression of phospholipid biosynthesis genes, but the mechanisms conducting Opi1p localization are not fully understood. A new study suggests the existence of a distinct pool of PA in the ER that is required for regulation of Opi1p localization and thus phospholipid metabolism in yeast.

Figure 1.

The Opi1p–Scs2p interaction is required for Opi1p translocation from the nucleus and for PA transport into the mitochondria. Gaspar et al. (6) propose that distinct pools of PA are present in the ER. One pool is associated with de novo synthesis of major phospholipids. A smaller pool is used for CL and DAG synthesis. DAG can either be acylated to TAG or used to synthesize PC via the Kennedy pathway. Exogenous choline competes for DAG through the Kennedy pathway and depletes the smaller pool of PA, which is required for Opi1p translocation from the nucleus, whereupon it binds to Scs2p and PA in the ER membrane. Additionally, the interaction of Opi1p with Scs2p is required for PA transfer to the mitochondria for CL synthesis.