Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Alters Mitochondrial Membrane Lipids

摘要: Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) has been shown to have selective antitumor activity. TRAIL induces ubiquitous pathways of cell death in which caspase activation is mediated either directly or via the release apoptogenic factors from mitochondria; however, precise components mitochondrial signaling pathway not well defined. Notably, mitochondria constitute an important target overcoming resistance many types tumors. Bid considered be fundamental engaging during receptor–mediated apoptosis, but this action dependent on lipids. Here, we report that alteration membrane lipids, particularly cardiolipin. This occurs independently and primes membranes proapoptotic Bid. We unveil a link between lipid homeostasis parallel apical does take over mode because concurrent caspase-8. In particular, TRAIL-induced lipids follows imbalance cellular phosphatidylcholine, results elevation diacylglycerol (DAG). Elevated DAG turn activates δ isoform phospholipid-dependent serine/threonine protein kinase C, then accelerates cleavage also show preservation phosphatidylcholine by inhibition lipid-degrading enzymes almost completely impedes pro-caspase-9 while scarcely changing