Nanoparticle triggered regulated necrosis (WP2513)

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 [ CPTAC Assay Portal]
last edited


Egonw, MaintBot, Bart Smeets, Mkutmon, Khanspers, Timverbruggen, and Laurent

Cited In


Homo sapiens


Adverse Outcome Pathways Nanomaterials Pathways


Pathway Ontology: nanomaterial response pathway necrosis pathway


Label Type Compact Identifier
Iron Metabolite hmdb:HMDB0000692
TNFR1 GeneProduct ensembl:ENSG00000067182
Necroptosis Pathway None
CASP8 GeneProduct ensembl:ENSG00000064012
TRADD GeneProduct ensembl:ENSG00000102871
ROS Metabolite chebi:26523
TRIF GeneProduct ensembl:ENSG00000127666
Arachidonic acid Metabolite hmdb:HMDB0001043
RIPK1 GeneProduct ensembl:ENSG00000137275
PAMPs Unknown None
FADD GeneProduct ensembl:ENSG00000168040
SMases Protein wikidata:Q413230
Calpains Protein None
Glutaminolysis Pathway wikidata:Q1532402
TNF Protein uniprot:P01375
Ge NP Metabolite chebi:30441
ATP Metabolite hmdb:HMDB0001532
Calcium Metabolite hmdb:HMDB0000464
Ceramide Metabolite chebi:17761
Nec-1 Metabolite pubchem.compound:2828334
PARP1 GeneProduct ensembl:ENSG00000143799
lipoxygenase Protein None
cPLA2 GeneProduct ensembl:ENSG00000116711
JNK GeneProduct ensembl:ENSG00000107643
RIPK3 GeneProduct ensembl:ENSG00000129465
TLRs Protein ensembl:Toll-like_receptor
Ferritin Protein uniprot:P02792
Labile iron pool Metabolite None
Glycogenolysis Pathway wikipathways:Glycogenolysis
Glycolysis Pathway wikipathways:Glycolysis
Iron Metabolite hmdb:HMDB0000692


  1. Ma Y-H, Huang C-P, Tsai J-S, Shen M-Y, Li Y-K, Lin L-Y. 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 Dec 15;207(3):258–69. PubMed Europe PMC Scholia
  2. Andón FT, Fadeel B. Programmed cell death: molecular mechanisms and implications for safety assessment of nanomaterials. Acc Chem Res. 2013 Mar 19;46(3):733–42. PubMed Europe PMC Scholia