title: Ceramide and apoptosis: exploring the enigmatic connections between sphingolipid metabolism and programmed cell death.
abstract: Programmed cell death, or apoptosis, is a complex process whereby eukaryotic cells react to physiologic or pathophysiologic stimuli by undergoing genetically programmed suicide. Programmed cell death involves many well-characterized signaling pathways including permeabilization of the mitochondrial outer membrane and activation of caspases. Other pathways, such as pro-apoptotic lipid signaling, are less understood despite many years of study. The sphingolipid ceramide has received considerable attention as a key regulator of programmed cell death, yet the mechanisms of its up-regulation and ability to control cell fate remain ill-defined. In this review, we will examine the connections between sphingolipid metabolism and programmed cell death with a focus on the role of de novo sphingolipid synthesis and sphingosine salvage in producing pro-apoptotic ceramide. We will also highlight the evidence supporting an increasingly complex role for ceramide in regulating apoptosis and provide a framework in which to ask new questions about the functions of this enigmatic lipid.
authors.affiliation: Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina 29401, USA.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Mullen
authors.forename: Lina M
authors.initials: LM
authors.lastname: Obeid
mesh_terms: D000818:Animals; D017209:Apoptosis; D002518:Ceramides / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D010088:Oxidoreductases / Q000378:metabolism; D051102:Serine C-Palmitoyltransferase / Q000378:metabolism; D015398:Signal Transduction; D013107:Sphingolipids / Q000737:chemistry / Q000378:metabolism*; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism
chemical_list: D002518:Ceramides; D013107:Sphingolipids; D010088:Oxidoreductases; C108138:dihydroceramide desaturase; D051102:Serine C-Palmitoyltransferase; D013108:Sphingomyelin Phosphodiesterase