Department of Medicine and Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY.
Ono Pharmaceutical Company, Ltd. Oncology Research Laboratories, Osaka, Japan.
J Lipid Res. 2019 Nov;60(11):1841-1850. doi: 10.1194/jlr.M094722. Epub 2019 Jun 26.
Sphingolipids contribute to the regulation of cell and tissue homeostasis, and disorders of sphingolipid metabolism lead to diseases such as inflammation, stroke, diabetes, and cancer. Sphingolipid metabolic pathways involve an array of enzymes that reside in specific subcellular organelles, resulting in the formation of many diverse sphingolipids with distinct molecular species based on the diversity of the ceramide (Cer) structure. In order to probe compartment-specific metabolism of sphingolipids in this study, we analyzed the Cer and SM species preferentially produced in the inner plasma membrane (PM), Golgi apparatus, ER, mitochondria, nucleus, and cytoplasm by using compartmentally targeted bacterial SMases and ceramidases. The results showed that the length of the acyl chain of Cer becomes longer according to the progress of Cer from synthesis in the ER to the Golgi apparatus, then to the PM. These findings suggest that each organelle shows different properties of SM-derived Cers consistent with its emerging distinct functions in vitro and in vivo.
鞘脂类参与细胞和组织稳态的调节，鞘脂代谢紊乱导致炎症、中风、糖尿病和癌症等疾病。鞘脂代谢途径涉及一系列位于特定亚细胞细胞器中的酶，导致形成许多不同的鞘脂，根据神经酰胺 (Cer) 结构的多样性具有不同的分子种类。为了在本研究中探测鞘脂的特定隔室代谢，我们使用隔室靶向性细菌鞘氨醇酶和神经酰胺酶分析了优先在质膜 (PM) 内层、高尔基体、内质网、线粒体、细胞核和细胞质中产生的 Cer 和 SM 种类。结果表明，Cer 的酰基链长度根据 Cer 在 ER 中的合成进展到高尔基体，然后到 PM 而变长。这些发现表明，每个细胞器都表现出不同的 SM 衍生 Cer 特性，与它在体外和体内出现的不同功能一致。
