RGD Reference Report - Novel pathway of ceramide production in mitochondria: thioesterase and neutral ceramidase produce ceramide from sphingosine and acyl-CoA. - Rat Genome Database

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Novel pathway of ceramide production in mitochondria: thioesterase and neutral ceramidase produce ceramide from sphingosine and acyl-CoA.

Authors: Novgorodov, Sergei A  Wu, Bill X  Gudz, Tatyana I  Bielawski, Jacek  Ovchinnikova, Tatiana V  Hannun, Yusuf A  Obeid, Lina M 
Citation: Novgorodov SA, etal., J Biol Chem. 2011 Jul 15;286(28):25352-62. doi: 10.1074/jbc.M110.214866. Epub 2011 May 25.
RGD ID: 13838796
Pubmed: PMID:21613224   (View Abstract at PubMed)
PMCID: PMC3137106   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M110.214866   (Journal Full-text)

Reports suggest that excessive ceramide accumulation in mitochondria is required to initiate the intrinsic apoptotic pathway and subsequent cell death, but how ceramide accumulates is unclear. Here we report that liver mitochondria exhibit ceramide formation from sphingosine and palmitoyl-CoA and from sphingosine and palmitate. Importantly, this activity was markedly decreased in liver from neutral ceramidase (NCDase)-deficient mice. Moreover, the levels of ceramide were dissimilar in liver mitochondria of WT and NCDase KO mice. These results suggest that NCDase is a key participant of ceramide formation in liver mitochondria. We also report that highly purified liver mitochondria have ceramidase, reverse ceramidase, and thioesterase activities. Increased accessibility of palmitoyl-CoA to the mitochondrial matrix with the pore-forming peptide zervamicin IIB resulted in 2-fold increases in palmitoyl-CoA hydrolysis by thioesterase. This increased hydrolysis was accompanied by an increase in ceramide formation, demonstrating that both outer membrane and matrix localized thioesterases can regulate ceramide formation. Also, ceramide formation might occur both in the outer mitochondrial membrane and in the mitochondrial matrix, suggesting the existence of distinct ceramide pools. Taken together, these results suggest that the reverse activity of NCDase contributes to sphingolipid homeostasis in this organelle in vivo.



Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Asah2Ratmitochondrion located_inIDA PMID:21613224UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Asah2  (N-acylsphingosine amidohydrolase 2)


Additional Information