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© Carmen Buchrieser, Marie-Christine Prevost
Legionella pneumophila et son flagelle, bactérie responsable de pneumopathie aigue grave. Bactérie de l'environnement , l'émergence récente de cette maladie s'explique par son affinité pour les systèmes modernes d'alimentation en eau comme les tours de refroidissement. Image colorisée.
Publication : The Journal of biological chemistry

Isoform-specific interaction of C-RAF with mitochondria

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in The Journal of biological chemistry - 20 Mar 2008

Galmiche A, Fueller J, Santel A, Krohne G, Wittig I, Doye A, Rolando M, Flatau G, Lemichez E, Rapp UR

Link to Pubmed [PMID] – 18356164

J. Biol. Chem. 2008 May;283(21):14857-66

The proteins of the RAF family (A-RAF, B-RAF, and C-RAF) are serine/threonine kinases that play important roles in development, mature cell regulation, and cancer. Although it is widely held that their localization on membranes is an important aspect of their function, there are few data that address this aspect of their mode of action. Here, we report that each member of the RAF family exhibits a specific distribution at the level of cellular membranes and that C-RAF is the only isoform that directly targets mitochondria. We found that the RAF kinases exhibit intrinsic differences in terms of mitochondrial affinity and that C-RAF is the only isoform that binds this organelle efficiently. This affinity is conferred by the C-RAF amino-terminal domain and does not depend on the presence of RAS GTPases on the surface of mitochondria. Finally, we analyzed the consequences of C-RAF activation on mitochondria and observed that this event dramatically changes their morphology and their subcellular distribution. Our observations indicate that: (i) RAF kinases exhibit different localizations at the level of cellular membranes; (ii) C-RAF is the only isoform that directly binds mitochondria; and (iii) through its functional coupling with MEK, C-RAF regulates the shape and the cellular distribution of mitochondria.

http://www.ncbi.nlm.nih.gov/pubmed/18356164