Pyruvate dehydrogenase dephosphorylation in rat brain synaptosomes and mitochondria: evidence for a calcium-mediated effect in response to depolarization, and variations due to ageing.
The phosphorylation state of P42, the phosphorylated, catalytically inactive, alpha-subunit of pyruvate dehydrogenase (PDH), decreased markedly (42.4%) in response to K(+)-depolarization of synaptosomes. The dephosphorylation was rapid (5-15 s), calcium-dependent and could also be observed in isolated mitochondria exposed to a rise in extramitochondrial calcium, suggesting that P42 dephosphorylation may act as a calcium sensor in the mitochondrial matrix. The depolarization-dependent dephosphorylation rate of P42 was decreased in synaptosomes derived from 24-month-old animals with respect to 3-month-old adults. The relevance of these results in terms of PDH activation during ageing is discussed.
Bogónez
E
E
Departamento de Biología Molecular, Centro de Biología Molecular, C.S.I.C., Universidad Autónoma de Madrid, Spain.
Gómez-Puertas
P
P
Satrústegui
J
J
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002118:Calcium / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D010766:Phosphorylation; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000201:enzymology*
D009419:Nerve Tissue Proteins; D009467:Neuromuscular Depolarizing Agents; D011768:Pyruvate Dehydrogenase Complex; D002118:Calcium