TY - JOUR
T1 - Probing compartment-specific sphingolipids with targeted bacterial sphingomyelinases and ceramidases
AU - Sakamoto, Wataru
AU - Canals, Daniel
AU - Salamone, Silvia
AU - Allopenna, Janet
AU - Clarke, Christopher J.
AU - Snider, Justin
AU - Obeid, Lina M.
AU - Hannun, Yusuf A.
N1 - Funding Information:
This work was supported in part by National Institutes of Health Grant CA97132 (Y.A.H.), a US Department of Veterans Affairs Merit Award (L.M.O.), and National Institute of General Medical Sciences Grant 9R01GM097741 (L.M.O.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Manuscript received 15 April 2019 and in revised form 11 June 2019. Published, JLR Papers in Press, June 26, 2019 DOI https://doi.org/10.1194/jlr.M094722
Publisher Copyright:
© 2019 American Society for Biochemistry and Molecular Biology Inc.. All rights reserved.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
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U2 - 10.1194/jlr.M094722
DO - 10.1194/jlr.M094722
M3 - Article
C2 - 31243119
AN - SCOPUS:85074377831
SN - 0022-2275
VL - 60
SP - 1841
EP - 1850
JO - Journal of Lipid Research
JF - Journal of Lipid Research
IS - 11
ER -