Lysosomal enzymes promote mitochondrial oxidant production, cytochrome c release and apoptosis

• DOI: 10.1046/j.1432-1033.2003.03765.x
• Publication Date: 2003-08-29T13:54:21Z
• Authors: Ming Zhao; Fernando Antunes; John W. Eaton; Ulf T. Brunk
• Keywords: Mitochondrial ROS

Exposure of mammalian cells to oxidant stress causes early (iron catalysed) lysosomal rupture followed by apoptosis or necrosis. Enhanced intracellular production reactive oxygen species (ROS), presumably mitochondrial origin, is also observed when are exposed nonoxidant pro‐apoptotic agonists cell death. We hypothesized that ROS generation in this latter case might promote the apoptotic cascade and could arise from effects released materials on mitochondria. Indeed, intact (J774 macrophages, HeLa AG1518 fibroblasts) lysosomotropic detergent O ‐methyl‐serine dodecylamide hydrochloride (MSDH) rupture, enhanced production, apoptosis. Furthermore, mixtures rat liver lysosomes mitochondria, selective MSDH promotes cytochrome c release, whereas has no direct effect purifed Intracellular associated with release (among other constituents) cathepsins activation phospholipase A2 (PLA2). find addition purified B D, PLA2, substantial increases PLA2 − but not D semipurified lysosomes, suggesting an amplification mechanism. Thus, initiation may involve constituents (such as D) leading further and, finally, release. Nonoxidant may, thus, act through mechanisms.