Free-radical-mediated fragmentation of monoamine oxidase in the mitochondrial membrane. Roles for lipid radicals.
A flux of hydroxyl radicals generated by gamma-irradiation can fragment monoamine oxidase in the membrane of submitochondrial particles. This fragmentation can be inhibited by mannitol and in addition is more extensive in monoamine oxidase preparations that have been depleted of lipid. This latter observation is consistent with the higher yields of fragmentation induced by hydroxyl radicals in soluble proteins in the absence of added lipids. In the absence of oxygen, gamma-irradiation of submitochondrial particles leads to cross-linking reactions. A flux of hydroperoxyl radicals also causes fragmentation, whereas one of superoxide is virtually inactive in this respect. The irradiation of submitochondrial particles leads in addition to the accumulation of products of lipid peroxidation. When these irradiated preparations are exposed to ferrous or cupric salts a further fragmentation of monoamine oxidase ensues, especially at acid pH. These transition-metal-catalysed reactions do not occur with irradiated preparations depleted of lipid, and the post-irradiation protein modifications are concomitant with further lipid peroxidation. The data indicate roles for lipid radicals in both fragmentation and cross-linking reactions of proteins in biological membranes. These reactions may have an important bearing on control of protein activity and of protein turnover in membranes.
D000818:Animals; D005609:Free Radicals; D007425:Intracellular Membranes / Q000187:drug effects / Q000201:enzymology; D007501:Iron / Q000494:pharmacology; D008563:Membrane Lipids / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology* / Q000528:radiation effects; D008995:Monoamine Oxidase / Q000378:metabolism* / Q000528:radiation effects; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D013367:Submitochondrial Particles / Q000201:enzymology
D005609:Free Radicals; D008563:Membrane Lipids; D007501:Iron; D008995:Monoamine Oxidase; D010100:Oxygen