PAH1

Pah1 is a gene in the yeast Saccharomyces cerevisiae that encodes the phosphatidic acid phosphatase Pah1p, a member of the lipin family. Pah1p catalyzes the hydrolysis of phosphatidic acid to diacylglycerol, directing flux from phospholipid synthesis toward triglyceride production and other lipid-derived metabolites. As such, Pah1p is a key node in yeast lipid metabolism, influencing the balance between membrane lipid synthesis and energy storage.

Regulation and localization: Pah1p activity is controlled by phosphorylation state. In yeast, the Nem1-Spo7 phosphatase complex dephosphorylates and activates Pah1p, promoting its association with the endoplasmic reticulum and nuclear envelope membranes. Kinases such as Pho85-Pho80 can maintain Pah1p in a more phosphorylated and less active form, altering its membrane binding and activity as needed by the cell.

Genetic and cellular consequences: Deletion or misregulation of PAH1 disrupts lipid homeostasis, often resulting in reduced diacylglycerol and triglyceride synthesis and accumulation of phosphatidic acid. This can lead to altered ER morphology, impaired nuclear membrane growth, and changes in autophagy or stress responses, reflecting the enzyme’s role in membrane biogenesis and lipid storage.

Relation to other organisms: Pah1p is the yeast homolog of the mammalian lipin proteins (LPIN1-3), sharing a common enzymatic activity and contributing to lipid metabolism and membrane biogenesis across eukaryotes.