Cookies Disclaimer

OK Our site saves small pieces of text information (cookies) on your device in order to deliver better content and for statistical purposes. You can disable the usage of cookies by changing the settings of your browser. By browsing our website without changing the browser settings you grant us permission to store that information on your device.

Publication

Bibliographic Data

  • Authors: Meuer, K.,Suppanz, I.E.,Lingor, P.,Planchamp, V.,Goericke, B.,Fichtner, L.,Braus, G.H.,Dietz, G.P.H.,Jakobs, S.,Baehr, M. and Weishaupt, J.H.
  • Title: Cyclin-dependent kinase 5 is an upstream regulator of mitochondrial fission during neuronal apoptosis
  • Journal: Cell Death Differ.
  • Volume: 14
  • Issue: 4
  • Volume: 651-661
  • DOI: 10.1038/sj.cdd.4402087

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.