THE EFFECTS OF SPHINGOLIPID METABOLISM AND ENDOPLASMIC RETICULUM STRESS ON INFLAMMATION

Abstract

The endoplasmic reticulum (ER) is an organelle found in all cells that is responsible for calcium (Ca2+) homeostasis, protein synthesis and lipid production. When the lumen of an ER has an overaccumulation of misfolded or unfolded proteins or a change occurs in the structure of the ER lipid membrane, ER stress occurs, in which the unfolded protein response (UPR) is activated. With many downstream targets, the UPR aims to fix the ER stress, either through pro-survival means or apoptotic cellular fate. Sphingolipids, a bioactive lipid that begin their synthesis in the ER, interact with and can affect ER stress. Due to their structure, they can affect the lipid bilayer and change the membrane fluidity. Sphingolipid signaling is also involved in cellular fate through ER stress. Both chronic ER stress and dysfunctions in sphingolipid metabolism contribute to the development of many pathologies, including inflammation. Signaling within both ER stress and sphingolipid metabolism have downstream targets that increase pro-inflammatory molecules within the body. This indicates that the interaction between sphingolipid metabolism and ER stress affect the activation of inflammation.