Protection against oxidant-mediated lysosomal rupture: a new anti-apoptotic activity of Bcl-2?

Bcl-2 antagonizes apoptosis through mechanisms which are not completely understood. We have proposed that apoptosis is initiated by minor lysosomal destabilization followed some time later by secondary massive lysosomal rupture. In J774 cells over-expressing Bcl-2, early oxidant-induced lysosomal destabilization is unaffected but secondary lysosomal rupture and apoptosis are suppressed, despite the fact that wild-type and Bcl-2 over-expressing cells degrade hydrogen peroxide at similar rates. It may be that Bcl-2 directly blocks the effects of released lysosomal enzymes and/or prevents downstream activation of unknown cytosolic pro-enzymes by released lysosomal hydrolases, suggesting a new and heretofore unknown activity of Bcl-2.