FEBS Letters
Volume 583, Issue 7 , Pages 1132-1140, 2 April 2009

Activation of c-Jun-N-terminal kinase and decline of mitochondrial pyruvate dehydrogenase activity during brain aging

Edited by Judit Ovádi

  • Qiongqiong Zhou

      Affiliations

    • Department of Cell Biology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205-2186, USA
    • ,
  • Philip Y. Lam

      Affiliations

    • Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90089-9121, USA
    • ,
  • Derick Han

      Affiliations

    • Research Center for Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9121, USA
    • ,
  • Enrique Cadenas

      Affiliations

    • Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089-9121, USA
    • Corresponding Author InformationCorresponding author.

Received 20 December 2008; received in revised form 13 February 2009; accepted 28 February 2009. published online 09 March 2009.

Abstract 

Mitochondrial dysfunction is often associated with aging and neurodegeneration. c-Jun-N-terminal kinase (JNK) phosphorylation and its translocation to mitochondria increased as a function of age in rat brain. This was associated with a decrease of pyruvate dehydrogenase (PDH) activity upon phosphorylation of the subunit of PDH. Phosphorylation of PDH is likely mediated by PDH kinase, the protein levels and activity of which increased with age. ATP levels were diminished, whereas lactic acid levels increased, thus indicating a shift toward anaerobic glycolysis. The energy transduction deficit due to impairment of PDH activity during aging may be associated with JNK signaling.

Keywords: Brain aging, Mitochondria, Pyruvate dehydrogenase, JNK, Neurodegeneration

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PII: S0014-5793(09)00172-0

doi:10.1016/j.febslet.2009.02.043

FEBS Letters
Volume 583, Issue 7 , Pages 1132-1140, 2 April 2009

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