Nanoparticle triggered regulated necrosis (WP2513)

Homo sapiens

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]


Egon Willighagen , Bart Smeets , Martina Summer-Kutmon , Kristina Hanspers , Tim Verbruggen , and Laurent Winckers


last edited

Discuss this pathway

Check for ongoing discussions or start your own.

Cited In

Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.


Homo sapiens


Adverse Outcome Pathways Nanomaterials Pathways


Pathway Ontology

nanomaterial response pathway necrosis pathway


Label Type Compact URI Comment
Iron Metabolite hmdb:HMDB0000692
ROS Metabolite chebi:26523
Arachidonic acid Metabolite hmdb:HMDB0001043
Ge NP Metabolite chebi:30441
ATP Metabolite hmdb:HMDB0001532
Calcium Metabolite hmdb:HMDB0000464
Ceramide Metabolite chebi:17761
Nec-1 Metabolite pubchem.compound:2828334
Iron Metabolite hmdb:HMDB0000692
TNFR1 GeneProduct ensembl:ENSG00000067182
CASP8 GeneProduct ensembl:ENSG00000064012
TRADD GeneProduct ensembl:ENSG00000102871
TRIF GeneProduct ensembl:ENSG00000127666
RIPK1 GeneProduct ensembl:ENSG00000137275
FADD GeneProduct ensembl:ENSG00000168040
PARP1 GeneProduct ensembl:ENSG00000143799
cPLA2 GeneProduct ensembl:ENSG00000116711
JNK GeneProduct ensembl:ENSG00000107643
RIPK3 GeneProduct ensembl:ENSG00000129465
SMases Protein wikidata:Q413230
TNF Protein uniprot:P01375
TLRs Protein ensembl:Toll-like_receptor
Ferritin Protein uniprot:P02792


  1. Water-soluble germanium nanoparticles cause necrotic cell death and the damage can be attenuated by blocking the transduction of necrotic signaling pathway. Ma YH, Huang CP, Tsai JS, Shen MY, Li YK, Lin LY. Toxicol Lett. 2011 Dec 15;207(3):258–69. PubMed Europe PMC Scholia
  2. Programmed cell death: molecular mechanisms and implications for safety assessment of nanomaterials. Andón FT, Fadeel B. Acc Chem Res. 2013 Mar 19;46(3):733–42. PubMed Europe PMC Scholia