Activation of c-Jun-N-terminal kinase and decline of mitochondrial pyruvate dehydrogenase activity during brain aging.
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 E(1alpha) 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.
Zhou
Qiongqiong
Q
Department of Cell Biology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205-2186, USA.
Lam
Philip Y
PY
Han
Derick
D
Cadenas
Enrique
E
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000375:Aging / Q000502:physiology*; D000693:Anaerobiosis / Q000502:physiology; D000818:Animals; D001921:Brain / Q000201:enzymology*; D020134:Catalytic Domain / Q000502:physiology; D006019:Glycolysis / Q000502:physiology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D010766:Phosphorylation / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D015398:Signal Transduction / Q000502:physiology*
D011768:Pyruvate Dehydrogenase Complex; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D048031:JNK Mitogen-Activated Protein Kinases