Sphingolipids, universal components of biological membranes of all eukaryotic organisms, from yeasts to mammals, in addition of playing a structural role, also play an important part of signal transduction pathways. They participate or, also, ignite several fundamental subcellular signaling processes but, more in general, they directly contribute to key biological activities such as cell motility, growth, senescence, differentiation as well as cell fate, i.e., survival or death. The sphingolipid metabolic pathway displays an intricate network of reactions that result in the formation of multiple sphingolipids, including ceramide, and sphingosine-1-phosphate. Different sphingolipids, that have key roles in determining cell fate, can induce opposite effects: as a general rule, sphingosine-1-phosphate promotes cell survival and differentiation, whereas ceramide is known to induce apoptosis. Furthermore, together with cholesterol, sphingolipids also represent the basic lipid component of lipid rafts, cholesterol- and sphingolipid-enriched membrane microdomains directly involved in cell death and survival processes. In this review, we briefly describe the characteristics of sphingolipids and lipid membrane microdomains. In particular, we will consider the involvement of various sphingolipids per se and of lipid rafts in apoptotic pathway, both intrinsic and extrinsic, in nonapoptotic cell death, in autophagy, and in cell differentiation. In addition, their roles in the most common physiological and pathological contexts either as pathogenetic elements or as biomarkers of diseases will be considered. We would also hint how the manipulation of sphingolipid metabolism could represent a potential therapeutic target to be investigated and functionally validated especially for those diseases for which therapeutic options are limited or ineffective.

中文翻译：

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关于鞘脂在细胞存活和死亡中的作用。

鞘脂，从酵母到哺乳动物，是所有真核生物生物膜生物膜的通用组成部分，除起结构作用外，还起信号转导途径的重要作用。它们参与或也点燃了几个基本的亚细胞信号传导过程，但更一般而言，它们直接促进关键的生物学活性，例如细胞运动，生长，衰老，分化以及细胞命运，即存活或死亡。鞘脂的代谢途径显示出复杂的反应网络，该反应导致形成多种鞘脂，包括神经酰胺和鞘氨醇-1-磷酸。在确定细胞命运中起关键作用的不同鞘脂可以诱导相反的作用：通常，1-磷酸鞘氨醇可促进细胞存活和分化，而已知神经酰胺会诱导细胞凋亡。此外，鞘脂与胆固醇一起也代表脂质筏，富含胆固醇和鞘脂的膜微区直接参与细胞死亡和存活过程的基本脂质成分。在这篇综述中，我们简要描述了鞘脂和脂质膜微区的特征。特别地，我们将考虑各种鞘脂本身和脂质筏参与内在和外在的凋亡途径，非凋亡性细胞死亡，自噬和细胞分化。此外，还将考虑它们在最常见的生理和病理环境中的作用，既可以作为致病因素，也可以作为疾病的生物标志物。