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Probing compartment-specific sphingolipids with targeted bacterial sphingomyelinases and ceramidases.
Journal of Lipid Research ( IF 6.5 ) Pub Date : 2019-06-26 , DOI: 10.1194/jlr.m094722
Wataru Sakamoto 1, 2 , Daniel Canals 1 , Silvia Salamone 1 , Janet Allopenna 1 , Christopher J Clarke 1 , Justin Snider 1 , Lina M Obeid 1, 3 , Yusuf A Hannun 4, 5
Affiliation  

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.

中文翻译:

用靶向细菌鞘磷脂酶和ceramidaidases探测隔室特异性鞘脂。

鞘脂有助于调节细胞和组织的动态平衡,并且鞘脂代谢紊乱导致诸如炎症,中风,糖尿病和癌症的疾病。鞘脂代谢途径涉及驻留在特定亚细胞细胞器中的一系列酶,基于神经酰胺(Cer)结构的多样性,导致形成具有不同分子种类的许多不同鞘脂。为了在这项研究中探测鞘脂的腔室特异性代谢,我们使用了针对性的隔室细菌SMases分析了内质膜(PM),高尔基体,ER,线粒体,细胞核和细胞质中优先产生的Cer和SM物种。 ceramidases。结果表明,随着Cer从ER合成到高尔基体,再到PM的进展,Cer的酰基链长度变长。这些发现表明,每个细胞器在体外和体内均显示出SM衍生的Cers的不同特性,与其新兴的独特功能相一致。
更新日期:2020-08-21
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