Skip to Main content Skip to Navigation
Journal articles

Sphingolipids distribution at mitochondria-associated membranes (MAM) upon induction of apoptosis.

Abstract : The levels and composition of sphingolipids and related metabolites are altered in aging and common disorders such as diabetes and cancers, as well as in neurodegenerative, cardiovascular, and respiratory diseases. Changes in sphingolipids have been implicated as being an essential step in mitochondria-driven cell death. However, little is known about the precise sphingolipid composition and modulation in mitochondria or related organelles. Here, we used LC-MS/MS to analyze the presence of key components of the ceramide metabolic pathway in vivo and in vitro in purified endoplasmic reticulum (ER), mitochondria-associated membranes (MAM), and mitochondria. Specifically, we analyzed the sphingolipids in the three pathways that generate ceramide: sphinganine in the de novo ceramide pathway, sphingomyelin in the breakdown pathway, and sphingosine in the salvage pathway. We observed sphingolipid profiles in mouse liver, mouse brain, and a human glioma cell line (U251). We analyzed the quantitative and qualitative changes of these sphingolipids during staurosporine (STS)-induced apoptosis in U251 cells. Ceramide, especially C16-ceramide, levels increased during early apoptosis possibly through a conversion from mitochondrial sphinganine and sphingomyelin, but sphingosine and lactosyl- and glucosyl-ceramide levels were unaffected. We also found that ceramide generation is enhanced in mitochondria when sphingomyelin levels are decreased in the MAM. This decrease was associated with an increase in acid sphingomyelinase (ASM) activity in MAM. We conclude that meaningful sphingolipid modifications occur in MAM, the mitochondria, and ER during the early phases of apoptosis.
Document type :
Journal articles
Complete list of metadatas

Cited literature [49 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-02625440
Contributor : Lisenn Lalier <>
Submitted on : Tuesday, May 26, 2020 - 2:33:20 PM
Last modification on : Friday, June 19, 2020 - 1:40:18 AM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

Collections

Citation

Vincent Mignard, Nolwenn Dubois, Didier Lanoé, Marie-Pierre Joalland, Lisa Oliver, et al.. Sphingolipids distribution at mitochondria-associated membranes (MAM) upon induction of apoptosis.. Journal of Lipid Research, American Society for Biochemistry and Molecular Biology, In press, pp.32350079. ⟨10.1194/jlr.RA120000628⟩. ⟨inserm-02625440⟩

Share

Metrics

Record views

39