| Literature DB >> 31176039 |
Zhihui Zhu1, Jianzhong Chen2, Guanghu Wang1, Ahmed Elsherbini1, Liansheng Zhong3, Xue Jiang4, Haiyan Qin1, Priyanka Tripathi1, Wenbo Zhi5, Stefka D Spassieva1, Andrew J Morris6, Erhard Bieberich7.
Abstract
The sphingolipid ceramide regulates beta-oxidation of medium and long chain fatty acids in mitochondria. It is not known whether it also regulates oxidation of very long chain fatty acids (VLCFAs) in peroxisomes. Using affinity chromatography, co-immunoprecipitation, and proximity ligation assays we discovered that ceramide interacts with Hsd17b4, an enzyme critical for peroxisomal VLCFA oxidation and docosahexaenoic acid (DHA) generation. Immunocytochemistry showed that Hsd17b4 is distributed to ceramide-enriched mitochondria-associated membranes (CEMAMs). Molecular docking and in vitro mutagenesis experiments showed that ceramide binds to the sterol carrier protein 2-like domain in Hsd17b4 adjacent to peroxisome targeting signal 1 (PTS1), the C-terminal signal for interaction with peroxisomal biogenesis factor 5 (Pex5), a peroxin mediating transport of Hsd17b4 into peroxisomes. Inhibition of ceramide biosynthesis induced translocation of Hsd17b4 from CEMAMs to peroxisomes, interaction of Hsd17b4 with Pex5, and upregulation of DHA. This data indicates a novel role of ceramide as a molecular switch regulating interaction of Hsd17b4 with Pex5 and peroxisomal function.Entities:
Keywords: Ceramide; Fatty acids; Peroxisomes
Mesh：
Substances：
Year: 2019 PMID： 31176039 PMCID： PMC6679753 DOI： 10.1016/j.bbalip.2019.05.017
Source DB: PubMed Journal: Biochim Biophys Acta Mol Cell Biol Lipids ISSN： 1388-1981 Impact factor: 4.698