STANDARD_NAME GALLUZZI_PERMEABILIZE_MITOCHONDRIA SYSTEMATIC_NAME M9642 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/GALLUZZI_PERMEABILIZE_MITOCHONDRIA NAMESPACE HUMAN_GENE_SYMBOL DESCRIPTION_BRIEF Proteins that permeabilize mitochondria. DESCRIPTION_FULL Mitochondria are vital for cellular bioenergetics and play a central role in determining the point-of-no-return of the apoptotic process. As a consequence, mitochondria exert a dual function in carcinogenesis. Cancer-associated changes in cellular metabolism (the Warburg effect) influence mitochondrial function, and the invalidation of apoptosis is linked to an inhibition of mitochondrial outer membrane permeabilization (MOMP). On theoretical grounds, it is tempting to develop specific therapeutic interventions that target the mitochondrial Achilles' heel, rendering cancer cells metabolically unviable or subverting endogenous MOMP inhibitors. A variety of experimental therapeutic agents can directly target mitochondria, causing apoptosis induction. This applies to a heterogeneous collection of chemically unrelated compounds including positively charged alpha-helical peptides, agents designed to mimic the Bcl-2 homology domain 3 of Bcl-2-like proteins, ampholytic cations, metals and steroid-like compounds. Such MOMP inducers or facilitators can induce apoptosis by themselves (monotherapy) or facilitate apoptosis induction in combination therapies, bypassing chemoresistance against DNA-damaging agents. In addition, it is possible to design molecules that neutralize inhibitor of apoptosis proteins (IAPs) or heat shock protein 70 (HSP70). Such IAP or HSP70 inhibitors can mimic the action of mitochondrion-derived mediators (Smac/DIABLO, that is, second mitochondria-derived activator of caspases/direct inhibitor of apoptosis-binding protein with a low isoelectric point, in the case of IAPs; AIF, that is apoptosis-inducing factor, in the case of HSP70) and exert potent chemosensitizing effects. PMID 16892093 GEOID AUTHORS Galluzzi L,Larochette N,Zamzami N,Kroemer G CONTRIBUTOR Arthur Liberzon CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Table 1 FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS ABL1,ANT,BAD,BAK,BAX,BBC3,BCL2,BCL2L1,BCL2L11,BID,BNIP3,CASP2,CASP3,CFL2,CLIC4,CPT2,DNM1L,FDXR,GCK,GSK3B,GZMA,GZMB,GZMC,HIST1H1C,JNK,LKB1,MCL1,MOAP1,MTCH2,NGFIB,NR4A1,P53AIP1,PLS3,PMAIP1,PPID,PRKCD,PRODH,SEK2,SERPINB5,SH3GLB1,SHC1,SIVA1,SOD2,TP53,TR3,VDAC1,VDAC2 GENE_SYMBOLS ABL1,,BAD,BAK1,BAX,BBC3,BCL2,BCL2L1,BCL2L11,BID,BNIP3,CASP2,CASP3,CFL2,CLIC4,CPT2,DNM1L,FDXR,GCK,GSK3B,GZMA,GZMB,,H1-2,MAPK8,STK11,MCL1,MOAP1,MTCH2,NR4A1,NR4A1,,PLS3,PMAIP1,PPID,PRKCD,PRODH,,SERPINB5,SH3GLB1,SHC1,SIVA1,SOD2,TP53,NR4A1,VDAC1,VDAC2 FOUNDER_NAMES