Universität zu Köln

Froehlich, M., Dejanovic, B., Kashkar, H., Schwarz, G. and Nussberger, S. (2014). S-palmitoylation represents a novel mechanism regulating the mitochondrial targeting of BAX and initiation of apoptosis. Cell Death Dis., 5. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-4889

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Abstract

The intrinsic pathway of apoptotic cell death is mainly mediated by the BCL-2-associated X (BAX) protein through permeabilization of the mitochondrial outer membrane (MOM) and the concomitant release of cytochrome c into the cytosol. In healthy, non-apoptotic cells, BAX is predominantly localized in the cytosol and exhibits a dynamic shuttle cycle between the cytosol and the mitochondria. Thus, the initial association with mitochondria represents a critical regulatory step enabling BAX to insert into MOMs, promoting the release of cytochrome c and ultimately resulting in apoptosis. However, the molecular mode of how BAX associates with MOMs and whether a cellular regulatory mechanism governs this process is poorly understood. Here we show that in both primary tissues and cultured cells, the association with MOMs and the proapoptotic action of BAX is controlled by its S-palmitoylation at Cys-126. A lack of BAX palmitoylation reduced BAX mitochondrial translocation, BAX oligomerization, caspase activity and apoptosis. Furthermore, ectopic expression of specific palmitoyl transferases in cultured healthy cells increases BAX S-palmitoylation and accelerates apoptosis, whereas malignant tumor cells show reduced BAX S-palmitoylation consistent with their reduced BAX-mediated proapoptotic activity. Our findings suggest that S-palmitoylation of BAX at Cys126 is a key regulatory process of BAX-mediated apoptosis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Froehlich, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Dejanovic, B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kashkar, H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwarz, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nussberger, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-446251
DOI:	10.1038/cddis.2014.17
Journal or Publication Title:	Cell Death Dis.
Volume:	5
Date:	2014
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2041-4889
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CYTOCHROME-C RELEASE; CELL-DEATH; BCL-2 PROTEIN; ACTIVATION; RECEPTOR; MEMBRANE; SITES; CA2+; UBIQUITINATION; IDENTIFICATION Multiple languages Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44625