Article

Cyclin-dependent kinase 5 is an upstream regulator of mitochondrial fission during neuronal apoptosis

Universitätsmedizin Göttingen, Göttingen, Lower Saxony, Germany
Cell Death and Differentiation (Impact Factor: 8.39). 05/2007; 14(4):651-61. DOI: 10.1038/sj.cdd.4402087
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ABSTRACT Under physiological conditions, mitochondrial morphology dynamically shifts between a punctuate appearance and tubular networks. However, little is known about upstream signal transduction pathways that regulate mitochondrial morphology. We show that mitochondrial fission is a very early and kinetically invariant event during neuronal cell death, which causally contributes to cytochrome c release and neuronal apoptosis. Using a small molecule CDK5 inhibitor, as well as a dominant-negative CDK5 mutant and RNAi knockdown experiments, we identified CDK5 as an upstream signalling kinase that regulates mitochondrial fission during apoptosis of neurons. Vice versa, our study shows that mitochondrial fission is a modulator contributing to CDK5-mediated neurotoxicity. Thereby, we provide a link that allows integration of CDK5 into established neuronal apoptosis pathways.

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Available from: Gunnar P H Dietz, Aug 24, 2015
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    • "Activation of Cdk5 plays an early role in the cell death cascade before the initiation of mitochondrial dysfunction, and Cdk5 inhibition prevents the mitochondrial damage and cell death caused by Prx2 inactivationmediated oxidative stress (Sun et al. 2008). Interestingly, Cdk5 also regulates mitochondrial fission during neuronal apoptosis as an upstream signaling kinase (Meuer et al. 2007). However, the precise mechanism by which Cdk5 regulates mitochondrial morphology is still unclear. "
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