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c-Jun N-terminal kinase (JNK)-mediated modulation of brain mitochondria function: new target proteins for JNK signalling in mitochondrion-dependent apoptosis

Schroeter, H., Boyd, C., Ahmed, R., Spencer, J., Duncan, R., Rice-Evans, C. and Cadenas, E. (2003) c-Jun N-terminal kinase (JNK)-mediated modulation of brain mitochondria function: new target proteins for JNK signalling in mitochondrion-dependent apoptosis. Biochemical Journal, 372 (2). pp. 359-369. ISSN 0264-6021

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To link to this item DOI: 10.1042/BJ20030201


The molecular mechanisms underlying the initiation and control of the release of cytochrome c during mitochondrion-dependent apoptosis are thought to involve the phosphorylation of mitochondrial Bcl-2 and Bcl-x(L). Although the c-Jun N-terminal kinase (JNK) has been proposed to mediate the phosphorylation of Bcl-2/Bcl-x(L) the mechanisms linking the modification of these proteins and the release of cytochrome c remain to be elucidated. This study was aimed at establishing interdependency between JNK signalling and mitochondrial apoptosis. Using an experimental model consisting of isolated, bioenergetically competent rat brain mitochondria, these studies show that (i) JNK catalysed the phosphorylation of Bcl-2 and Bcl-x(L) as well as other mitochondrial proteins, as shown by two-dimensional isoelectric focusing/SDS/PAGE; (ii) JNK-induced cytochrome c release, in a process independent of the permeability transition of the inner mitochondrial membrane (imPT) and insensitive to cyclosporin A; (iii) JNK mediated a partial collapse of the mitochondrial inner-membrane potential (Deltapsim) in an imPT- and cyclosporin A-independent manner; and (iv) JNK was unable to induce imPT/swelling and did not act as a co-inducer, but as an inhibitor of Ca-induced imPT. The results are discussed with regard to the functional link between the Deltapsim and factors influencing the permeability transition of the inner and outer mitochondrial membranes. Taken together, JNK-dependent phosphorylation of mitochondrial proteins including, but not limited to, Bcl-2/Bcl-x(L) may represent a potential of the modulation of mitochondrial function during apoptosis.

Item Type:Article
Divisions:Life Sciences > School of Chemistry, Food and Pharmacy > Department of Food and Nutritional Sciences > Human Nutrition Research Group
ID Code:18619
Uncontrolled Keywords:Animals *Apoptosis Brain/*drug effects/metabolism Cyclosporine/pharmacology Cytochrome c Group/*metabolism Electrophoresis, Gel, Two-Dimensional Enzyme Inhibitors/pharmacology Intracellular Membranes JNK Mitogen-Activated Protein Kinases MAP Kinase Signaling System Male Membrane Potentials Mitochondria/*drug effects/metabolism Mitochondrial Swelling Mitogen-Activated Protein Kinases/*pharmacology Phosphorylation Proto-Oncogene Proteins c-bcl-2/*metabolism Rats Rats, Wistar Signal Transduction bcl-X Protein
Additional Information:Schroeter, Hagen Boyd, Clinton S Ahmed, Ruhi Spencer, Jeremy P E Duncan, Roger F Rice-Evans, Catherine Cadenas, Enrique R01-AG16718/AG/NIA NIH HHS/United States R01-ES11342/ES/NIEHS NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. England The Biochemical journal Biochem J. 2003 Jun 1;372(Pt 2):359-69.
Publisher:Portland Press Limited

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