The Implications for Cells of the Lipid Switches Driven by Protein–Membrane Interactions and the Development of Membrane Lipid Therapy

Abstract

The cell membrane contains a variety of receptors that interact with signaling molecules. However, agonist–receptor interactions not always activate a signaling cascade. Amphitropic membrane proteins are required for signal propagation upon ligand-induced receptor activation. These proteins localize to the plasma membrane or internal compartments; however, they are only activated by ligand-receptor complexes when both come into physical contact in membranes. These interactions enable signal propagation. Thus, signals may not propagate into the cell if peripheral proteins do not co-localize with receptors even in the presence of messengers. As the translocation of an amphitropic protein greatly depends on the membrane’s lipid composition, regulation of the lipid bilayer emerges as a novel therapeutic strategy. Some of the signals controlled by proteins non-permanently bound to membranes produce dramatic changes in the cell’s physiology. Indeed, changes in membrane lipids induce translocation of dozens of peripheral signaling proteins from or to the plasma membrane, which controls how cells behave. We called these changes “lipid switches”, as they alter the cell’s status (e.g., proliferation, differentiation, death, etc.) in response to the modulation of membrane lipids. Indeed, this discovery enables therapeutic interventions that modify the bilayer’s lipids, an approach known as membrane-lipid therapy (MLT) or melitherapy.

The Novel Antitumor Compound HCA Promotes Glioma Cell Death by Inducing Endoplasmic Reticulum Stress and Autophagy

“…These clinically relevant pharmaceutical activities of natural hydroxylated fatty acids encouraged us to produce HCA and test its properties [ 43 ]. The design of HCA was encompassed in the sphere of melitherapy, a therapeutic approach that regulates the composition and structure of cell membranes as a means to treat different pathologies [ 6 , 44 ]. One example of a compound based on this approach is 2OHOA, a hydroxylated derivative of oleic acid that has an important potential in combatting different types of cancer [ 45 ].…”

Unexpected Role of Sterol Synthesis in RNA Stability and Translation in Leishmania

“…However, during the last few decades, a substantial amount of research revealed the importance of lipids as signaling molecules regulating many processes and gene expression pathways in the cell. Sphingolipids and their metabolites, such as ceramides, sphingosine and sphingosine-1-phosphate (S1P), regulate cellular processes, including proliferation, differentiation and cell death [ 60 , 61 , 62 ]. The S1P acts extracellularly through cell surface receptors.…”

Unexpected Role of Sterol Synthesis in RNA Stability and Translation in Leishmania

“…However, during last two decades a substantial amount of research revealed the importance of lipids as signaling molecules regulating many processes and gene expression pathways in the cell. Sphingolipids and their metabolites such as ceramides, sphingosine and sphingosine-1-phosphate (S1P) regulate cellular processes including proliferation, differentiation and cell death [60][61][62]. The S1P acts extracellularly through cell surface receptors.…”