The targeting of plasmalemmal ceramide to mitochondria during apoptosis

Babiychuk, Eduard B.; Atanassoff, Alexander P.; Monastyrskaya, Katia; Brandenberger, Christina; Studer, Daniel; Allemann, Catherine; Draeger, Annette (2011). The targeting of plasmalemmal ceramide to mitochondria during apoptosis. PLoS ONE, 6(8), e23706. Lawrence, Kans.: Public Library of Science 10.1371/journal.pone.0023706

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Ceramide is a key lipid mediator of cellular processes such as differentiation, proliferation, growth arrest and apoptosis. During apoptosis, ceramide is produced within the plasma membrane. Although recent data suggest that the generation of intracellular ceramide increases mitochondrial permeability, the source of mitochondrial ceramide remains unknown. Here, we determine whether a stress-mediated plasmalemmal pool of ceramide might become available to the mitochondria of apoptotic cells. We have previously established annexin A1--a member of a family of Ca(2+) and membrane-binding proteins--to be a marker of ceramide platforms. Using fluorescently tagged annexin A1, we show that, upon its generation within the plasma membrane, ceramide self-associates into platforms that subsequently invaginate and fuse with mitochondria. An accumulation of ceramide within the mitochondria of apoptotic cells was also confirmed using a ceramide-specific antibody. Electron microscopic tomography confirmed that upon the formation of ceramide platforms, the invaginated regions of the plasma membrane extend deep into the cytoplasm forming direct physical contacts with mitochondrial outer membranes. Ceramide might thus be directly transferred from the plasma membrane to the mitochondrial outer membrane. It is conceivable that this "kiss-of-death" increases the permeability of the mitochondrial outer membrane thereby triggering apoptosis.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Cell Biology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy

UniBE Contributor:

Babiychuk, Eduard and Studer, Daniel Franz

ISSN:

1932-6203

Publisher:

Public Library of Science

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:17

Last Modified:

10 Dec 2014 11:03

Publisher DOI:

10.1371/journal.pone.0023706

PubMed ID:

21886813

Web of Science ID:

000294128100026

BORIS DOI:

10.7892/boris.5111

URI:

https://boris.unibe.ch/id/eprint/5111 (FactScience: 209829)

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