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Free Radic Biol Med. 2012 Feb 15;52(4):757-64. doi: 10.1016/j.freeradbiomed.2011.11.030. Epub 2011 Dec 16.

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

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1
Section of Medical Biochemistry, Department of Basic Medical Sciences, University of Bari, Bari, Italy.

Abstract

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 β-adrenoceptor agonists in preventing/reversing the detrimental effects of oxidative stress in the mitochondrial respiratory system.

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