Abstract
Among the cellular lipids, phosphatidic acid (PA) is a peculiar one as it is at the same time a key building block of phospholipid synthesis and a major lipid second messenger conveying signaling information. The latter is thought to largely occur through the ability of PA to recruit and/or activate specific proteins in restricted compartments and within those only at defined submembrane areas. Furthermore, with its cone-shaped geometry PA locally changes membrane topology and may thus be a key player in membrane trafficking events, especially in membrane fusion and fission steps, where lipid remodeling is believed to be crucial. These pleiotropic cellular functions of PA, including phospholipid synthesis and homeostasis together with important signaling activity, imply that perturbations of PA metabolism could lead to serious pathological conditions. In this mini-review article, after outlining the main cellular functions of PA, we highlight the different neurological diseases that could, at least in part, be attributed to an alteration in PA synthesis and/or catabolism.
Highlights
Phosphatidic acid (PA) is a low abundant phospholipid of membranes that, constitutes the original building block from which most glycerophospholipids are synthesized, plays an important structural task
The diversity of mechanisms of phosphatidic acid (PA) signaling and physiological functions mostly relies on the fact that PA is synthesized by a complex set of different enzymes involved in diverse array of pathways
phospholipases D (PLD), DGKs, and LPAATs each constitute a big collection of isoenzymes differently localized within cells and displaying cell type specificity
Summary
Phosphatidic acid (PA) is a low abundant phospholipid of membranes that, constitutes the original building block from which most glycerophospholipids are synthesized, plays an important structural task. Structural PA results from two successive acylation reactions (Figure 1). Hydrolysis of the distal phosphodiester bond in phospholipids by phospholipases D (PLD) constitutes the second pathway (Figure 1). Six different PLDs have been identified in mammals, only PLD1/2 and PLD6 have been shown to synthesize PA from phosphatidylcholine (PC) and cardiolipin (CL), respectively (Jang et al, 2012). PA is composed of a glycerol backbone esterified with two fatty acyl chains at positions C-1 and C-2, and with a phosphate at position C-3. The latter confers the specific features of PA compared to the other diacyl–glycerophospholipids. These two characteristics enable PA both to
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
