More recently, it has been found that this class of lipids is associated with several human pathologies linked to apoptosis dysfunction, such as cancer and neurodegenerative diseases ( Ozbayraktar & Ulgen, 2009 Hla & Dannenberg, 2012 Morad & Cabot, 2013). Sphingolipids are now known to be important in cellular responses to many different stimuli, acting as messengers in a variety of signalling pathways that control cellular processes such as senescence, differentiation, apoptosis, cell cycle arrest, proliferation, mitogenesis, inflammation, migration and angiogenesis ( Hannun & Obeid, 2008). Subsequently, Hannun and co-workers showed that this pathway could be activated by receptor-mediated mechanisms ( Okazaki et al., 1989) and demonstrated that ceramide is a second messenger ( Okazaki et al., 1990). However, the pioneer work of the Kolesnick laboratory reported for the first time the rapid sphingomyelinase (SMase) activation in response to 1,2-diacylglycerols ( Kolesnick, 1987) and proposed the existence of an SMase-based signalling pathway ( Kolesnick & Clegg, 1988 Kolesnick, 1989). The LCB (typically the 18-carbon amino alcohol sphingosine) may have a double bond (sphingosine), no double bond (dihydrosphingosine), be hydroxylated at the C4 position (phytosphingosine) or several head groups designated R at the C1 position (see list).įor a long time, sphingolipids were considered molecules with an exclusively structural role in membranes. Sphingolipid structure consists of a LCB, which can be linked to a fatty acid via an amide bond and to a polar head. The building blocks and structural diversity of sphingolipids. It can be anticipated that studies using this model system will further unravel mechanisms underlying the regulation of apoptosis by sphingolipids and contribute to novel therapeutic strategies against serious human diseases associated with dysfunction of sphingolipid-dependent cell death programmes.
Although yeast is undeniably a simple model, the conservation of the sphingolipid metabolism and of the core machinery engaged in regulated cell death has already provided valuable clues to the understanding of metabolic pathways involved in distinct cellular processes, including apoptosis. However, the peculiarities of this class of bioactive lipids, namely the interconnectivity of their metabolic pathways, the specific subcellular localization where they are generated and the transport mechanisms involved, introduce a considerably high level of complexity in deciphering their role in the signalling and regulation of programmed cell death. It has been established that sphingolipids are engaged in the regulation of apoptosis both as direct executors and as signalling molecules.
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