Activation of the cAMP cascade in human fibroblast cultures rescues the activity of oxidatively damaged complex I

作者：De Rasmo Domenico; Signorile Anna; Larizza Maria; Pacelli Consiglia; Cocco Tiziana; Papa Sergio^*

来源：Free Radical Biology and Medicine, 2012, 52(4): 757-764.

DOI：10.1016/j.freeradbiomed.2011.11.030

• Complex I
• cAMP cascade
• beta-Agonist
• Mitochondria
• Protein carbonylation
• Free radicals

A study of the relationship between cAMP/PKA-dependent phosphorylation and oxidative damage of subunits of complex I of the mitochondrial respiratory chain is presented. It is shown that, in fibroblast cultures, PKA-mediated phosphorylation of the NDUFS4 subunit of complex I rescues the activity of the oxidatively damaged complex. Evidence is presented showing that this effect is mediated by phosphorylation-dependent exchange of carbonylated NDUFS4 subunit in the assembled complex with the de novo synthesized subunit. These results indicate a potential use for beta-adrenoceptor agonists in preventing/reversing the detrimental effects of oxidative stress in the mitochondrial respiratory system.

• 出版日期2012-2-15