Free Radical and Iron-Mediated Injury in Lysosomes

Abstract

Considerable morphological evidence suggests that the loss of lysosomal membrane integrity occurs during experimental ischemia (1,2), however, whether the released hydrolases play an essential role prior to irreversible injury remains unclear. In recent years, increasing evidence has accumulated demonstrating that myocardial ischemia and reperfusion result in excessive production of oxygen radicals (3–5). Thus, free radical-mediated lipid peroxidation has been implicated to play a significant role in the pathogenesis of myocardial ischemic reperfusion injury. At the subcellular level, the phospholipid-rich lysosomal membrane is a potential site of free radical attack. In the present report, we summarize our recent studies of free radical reactions in lysosomes. In an effort to circumvent the technical difficulties of investigating free radical reactions in situ, we designed in vitro experiments using isolated lysosomes. The temporal relationship of the susceptibility of lysosomal membranes to oxygen radicals and the subsequent changes in lysosomal size and membrane integrity were studied.