title: Fluid levity of the cell: Role of membrane lipid architecture in genetic sphingolipidoses.
abstract: Sphingolipidoses arise from inherited loss of function of key enzymes regulating the sphingolipid (SL) metabolism and the accumulation of large quantities of these lipids in affected cells. Most frequently, toxicity is manifested in the nervous system, where survival and function of neurons and glial cells are most affected. Although detailed information is available on neuroglial alterations during terminal stages of the disease, the initial pathogenic mechanisms triggering neuropathology are largely unclear. Because they are key components of biological membranes, changes in the local concentration of SLs are likely to impact the organization of membrane domains and functions. This Commentary proposes that SL toxicity involves initial defects in the integrity of lipid domains, membrane fluidity, and membrane bending, leading to membrane deformation and deregulation of cell signaling and function. Understanding how SLs alter membrane architecture may provide breakthroughs for more efficient treatment of sphingolipidoses. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Anatomy and Cell Biology, University of Illinois, Chicago, Illinois. dauria@uic.edu.
authors.forename: Ludovic
authors.identifier: 0000-0001-6270-7739
authors.initials: L
authors.lastname: D'Auria
authors.affiliation: Department of Anatomy and Cell Biology, University of Illinois, Chicago, Illinois. ebongarz@uic.edu.
authors.forename: Ernesto R
authors.initials: ER
authors.lastname: Bongarzone
mesh_terms: D000818:Animals; D006801:Humans; D008560:Membrane Fluidity / Q000502:physiology*; D008563:Membrane Lipids / Q000172:deficiency / Q000235:genetics*; D013106:Sphingolipidoses / Q000235:genetics* / Q000473:pathology*
chemical_list: D008563:Membrane Lipids
keywords: Krabbe's disease; caveolin; fluidity; lipid rafts; neurodegeneration; psychosine; sphingolipids