Phosphatidic acid: from biophysical properties to diverse functions

Phosphatidic acid (PA), the simplest phospholipid, acts as a key metabolic intermediate and second messenger that impacts diverse cellular and physiological processes across species ranging from microbes to plants and mammals. The cellular levels of PA dynamically change in response to stimuli, and multiple enzymatic reactions can mediate its production and degradation. PA acts as a signalling molecule and regulates various cellular processes via its effects on membrane tethering, enzymatic activities of target proteins, and vesicular trafficking. Because of its unique physicochemical properties compared to other phospholipids, PA has emerged as a class of new lipid mediators influencing membrane structure, dynamics, and protein interactions. This review summarizes the biosynthesis, dynamics, and cellular functions and properties of PA. Phosphatidic acid (PA) plays an important role in cell fate determination, cytoskeleton remodeling, exocytosis, receptor endocytosis, membrane trafficking, and homeostasis of organelles. The electrostatic attraction is the basis of the interaction of PA and proteins, and the second ionizable proton can further enhance their interaction. The cone shape of PA results in a loosened structure around PA and exposure of the hydrophobic zone to the effector proteins.