ENHANCED ENZYMATIC DEGRADATION OF RADICAL DAMAGED MITOCHONDRIAL-MEMBRANE COMPONENTS

The location of a protein (soluble or membrane-bound) influences the e xtent of oxidative damage caused by free radicals. It has been establi shed that after radical attack, soluble proteins can become more susce ptible to hydrolysis by individual proteinases than native proteins.1- 4 We have now examined the hydrolytic susceptibility following radical attack of a protein that is located within a membrane environment, mi tochondrial monoamine oxidase (MAO). After exposure to oxygen radicals generated by gamma irradiation, hydrolysis of sub-mitochondrial parti cles (SMP) containing MAO was increased in three respects. First, the generation of small fragments of MAO by the proteinases elastase and t rypsin, was enhanced. Second, the generation by these enzymes and by p hospholipase A2 of non-sedimentable membrane fragments containing MAO was also increased. Third, autolysis of SMP was enhanced. Hence, prote ins located within membranes may become more susceptible to enzymatic degradation following oxidative damage.