title: Sphingolipids in mitochondria.
abstract: Sphingolipids are bioactive lipids found in cell membranes that exert a critical role in signal transduction. In recent years, it has become apparent that sphingolipids participate in growth, senescence, differentiation and apoptosis. The anabolism and catabolism of sphingolipids occur in discrete subcellular locations and consist of a strictly regulated and interconnected network, with ceramide as the central hub. Altered sphingolipid metabolism is linked to several human diseases. Hence, an advanced knowledge of how and where sphingolipids are metabolized is of paramount importance in order to understand the role of sphingolipids in cellular functions. In this review, we provide an overview of sphingolipid metabolism. We focus on the distinct pathways of ceramide synthesis, highlighting the mitochondrial ceramide generation, transport of ceramide to mitochondria and its role in the regulation of mitochondrial-mediated apoptosis, mitophagy and implications to disease. We will discuss unanswered questions and exciting future directions. This article is part of a Special Issue entitled: Lipids of Mitochondria edited by Guenther Daum.
authors.affiliation: Stony Brook Cancer Center and the Department of Medicine, Stony Brook University, Health Sciences Center, Stony Brook, NY 11794, USA.
authors.forename: María José
authors.initials: MJ
authors.lastname: Hernández-Corbacho
authors.affiliation: Stony Brook Cancer Center and the Department of Medicine, Stony Brook University, Health Sciences Center, Stony Brook, NY 11794, USA; Department of Biochemistry, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt.
authors.forename: Mohamed F
authors.initials: MF
authors.lastname: Salama
authors.affiliation: Stony Brook Cancer Center and the Department of Medicine, Stony Brook University, Health Sciences Center, Stony Brook, NY 11794, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Canals
authors.affiliation: Stony Brook Cancer Center and the Department of Medicine, Stony Brook University, Health Sciences Center, Stony Brook, NY 11794, USA.
authors.forename: Can E
authors.initials: CE
authors.lastname: Senkal
authors.affiliation: Stony Brook Cancer Center and the Department of Medicine, Stony Brook University, Health Sciences Center, Stony Brook, NY 11794, USA; The Northport VA Medical Center, Northport, NY 11768, USA. Electronic address: Lina.Obeid@stonybrookmedicine.edu.
authors.forename: Lina M
authors.initials: LM
authors.lastname: Obeid
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D063306:Mitophagy / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013107:Sphingolipids / Q000378:metabolism*
chemical_list: D002518:Ceramides; D013107:Sphingolipids
keywords: Cancer; Ceramide; Mitochondrial apoptosis; Mitophagy; Sphingolipid metabolism