, 2008; Lodish et al., 2012). Nevertheless, lipid signaling is

not restricted to the constituents of the cytosolic monolayer of plasma membranes. Following cleavage, phospholipids in the outer monolayer are involved in the generation of diacylglycerol, sphingolipids, fatty acids, and molecules derived from Everolimus such lipids, which act as important mediators of biological activities (Futerman, 2007; Alberts et al., 2008; Lodish et al., 2012). Additionally, membrane phospholipid asymmetry, together with the translocation of phosphatidylserine to the extracellular monolayer of the plasma membrane, acts as a cell surface signal for apoptotic cells to be phagocytosed (Verhoven et al., 1995; Alberts et al., 2008; Lodish et al., 2012).

In several types of lipid-dependent cell signaling, phospholipids must be cleaved through the action of different classes of phospholipases, which cleave ester bonds (e.g., isoforms of phospholipase-A1, phospholipase-A2 and phospholipase-B) or phosphoester bonds (e.g., isoforms of phospholipase-C and phospholipase-D), generating modified phospholipid acyl or phospholipid head groups that are directly or indirectly modified and act as extracellular or intracellular mediators (Alberts et al., 2008; Nelson and Cox, 2009; Lodish et al., 2012; Aloulou et al., 2012). Among the different classes of phospholipases, the phospholipase-D class has been receiving special attention in the literature based on the biological activities of these molecules. These enzymes exhibit a broad distribution in nature and Venetoclax have been described

in different organisms, such as viruses, bacteria, plants, yeasts, invertebrates and mammals (Jenkins and Frohman, 2005; Raghu et al., 2009). Phospholipase-D catalyzes the hydrolysis of glycerophospholipids or sphingophospholipids, generating phosphatidic acid, lysophosphatidic 3-mercaptopyruvate sulfurtransferase acid, ceramide 1-phosphate plus choline or other hydrophilic molecules, such as serine, inositol, and ethanolamine. The phosphatidic acid originating in the cellular environment is metabolically converted into diacylglycerol and/or lysophosphatidic acid, while ceramide 1-phosphate is converted in sphingosine 1-phosphate. Both of these molecules can act as second messengers within cells, contributing to the effects of phospholipase-D (Anliker and Chun, 2004; Chalfant and Spiegel, 2005). Several signaling cascades have been described involving these lipid-derived metabolites and their specific membrane receptors. These bioactive lipids are known to activate different signaling pathways in different cells and stimulate various physiological and pathophysiological changes, such as inflammatory responses, platelet aggregation, increased vascular permeability, and cell proliferation and death, among other alterations (Anliker and Chun, 2004).