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Activation of c-Jun-N-terminal kinase and decline of mitochondrial pyruvate dehydrogenase activity during brain aging |
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| Authors: | Qiongqiong Zhou Derick Han |
| Institution: | a Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90089-9121, USA b Department of Cell Biology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205-2186, USA c Research Center for Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9121, USA d Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089-9121, USA |
| 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 E1α 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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