Programmed cell death: regulated necrosis. During regulated necrosis, different stimuli are recognized or sensed by specific receptors on the cell surface or inside cells. The activation of the necrosome stimulates different signaling pathways leading to mitochondrial hyperpolarization, lysosomal membrane permeabilization, and generation of reactive oxygen species (ROS), leading to cellular disintegration. A recent study revealed that germanium nanoparticles trigger necrostatin-1-inhibitable cell death with a reduction of the mitochondrial membrane potential. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP2513 CPTAC Assay Portal] b1c d9c nanomaterial response pathway PW:0001435 Pathway Ontology necrosis pathway PW:0000279 Pathway Ontology 22720979 PubMed Programmed Cell Death: Molecular Mechanisms and Implications for Safety Assessment of Nanomaterials. Acc Chem Res 2012 Andón FT Fadeel B 21979174 PubMed Water-soluble germanium nanoparticles cause necrotic cell death and the damage can be attenuated by blocking the transduction of necrotic signaling pathway. Toxicol Lett 2011 Ma YH Huang CP Tsai JS Shen MY Li YK Lin LY