2025
Molecular mechanisms of immune cell death in immunosenescence
Verduijn J, Coutant K, Fane M, Galluzzi L. Molecular mechanisms of immune cell death in immunosenescence. Cell Death & Differentiation 2025, 1-8. PMID: 40550879, DOI: 10.1038/s41418-025-01535-2.Peer-Reviewed Original ResearchActivation of regulated cell deathCell deathOrganismal agingImmune cell deathBone marrow defectImmune cell populationsImmune cell typesContext of immunosenescenceMolecular mechanismsNumerical alterationsThymic involutionMarrow defectCell typesImmune homeostasisImmune systemUnscheduled activitiesCell populationsImmunosenescenceFunctional degenerationMultiple compartmentsDeathMetabolic switches in cell death regulation
Galluzzi L. Metabolic switches in cell death regulation. Cell Metabolism 2025, 37: 1252-1254. PMID: 40466623, DOI: 10.1016/j.cmet.2025.04.017.Peer-Reviewed Original ResearchPIP5K1A Suppresses Ferroptosis and Induces Sorafenib Resistance by Stabilizing NRF2 in Hepatocellular Carcinoma
Guo M, Chen S, Sun J, Xu R, Qi Z, Li J, Zhou L, Fang Y, Liu T, Xia J. PIP5K1A Suppresses Ferroptosis and Induces Sorafenib Resistance by Stabilizing NRF2 in Hepatocellular Carcinoma. Advanced Science 2025, e04372. PMID: 40405713, DOI: 10.1002/advs.202504372.Peer-Reviewed Original ResearchNrf2-dependent transcriptionHepatocellular carcinomaKinase-independent mannerProgrammed cell deathKelch domain of Kelch-like ECH-associated protein 1Sensitizes HCC cells to sorafenibHepatocellular carcinoma tumorigenesisIron-dependent formInduced sorafenib resistanceKelch domainPIP5K1AKelch-like ECH-associated protein 1Inhibit HCC growthCells to sorafenibECH-associated protein 1Cell deathSorafenib-induced ferroptosisEfficacy of sorafenibHepatocellular carcinoma patientsFerroptosis resistanceCancer-related mortalityUbiquitination degradationFerroptosis inducersProtein 1Stabilize Nrf2PLK4 inhibition as a strategy to enhance non-small cell lung cancer radiosensitivity.
Dominguez-Vigil I, Banik K, Baro M, Contessa J, Hayman T. PLK4 inhibition as a strategy to enhance non-small cell lung cancer radiosensitivity. Molecular Cancer Therapeutics 2025, of1-of12. PMID: 40296663, DOI: 10.1158/1535-7163.mct-24-0978.Peer-Reviewed Original ResearchNon-small cell lung cancerLung cancerCFI-400945Mitotic catastropheNon-small cell lung cancer radiosensitizationRadiosensitivity of NSCLC cell linesCentrosome amplificationRadiation-induced tumor growth delayPLK4 inhibitionCell deathCurative-intent chemoradiationIncreased G2/M cell cycle arrestPolo-like kinase 4Subtype of lung cancerCell lung cancerIncreased centrosome amplificationCancer-related mortalityG2/M cell cycle arrestNSCLC cell linesCell cycle phase distributionClinical trial evaluationTargeting PLK4NSCLC in vitroCell cycle arrestPotential therapeutic targetBlocking Nitrosylation Induces Immunogenic Cell Death by Sensitizing NRAS-Mutant Melanoma to MEK Inhibitors
Srivastava J, Yadav V, Jimenez R, Phadatare P, Inamdar N, Young M, Bacchiocchi A, Halaban R, Fang B, de Mingo Pulido A, Tsai K, Smalley K, Koomen J, Rodriguez P, Premi S. Blocking Nitrosylation Induces Immunogenic Cell Death by Sensitizing NRAS-Mutant Melanoma to MEK Inhibitors. Cancer Research 2025, 85: 2268-2287. PMID: 40287947, PMCID: PMC12167936, DOI: 10.1158/0008-5472.can-24-0693.Peer-Reviewed Original ResearchConceptsInduce immunogenic cell deathNRAS-mutant melanomaDamage-associated molecular patternsImmunogenic cell deathMEK inhibitorsDendritic cellsRepertoire of CD8+ T cellsCocultures of dendritic cellsCD8+ T cellsCell deathActivating NRAS mutationsAntimelanoma immune responsesImmunocompetent mouse modelInnovative treatment strategiesMEK-ERK signalingAntitumor immunityNRAS mutationsMelanoma subtypesERK MAPK pathwayTargeted therapyTumor microenvironmentT cellsT lymphocytesMelanoma growthTherapeutic resistanceThe diversity of CD8+ T cell dysfunction in cancer and viral infection
Galluzzi L, Smith K, Liston A, Garg A. The diversity of CD8+ T cell dysfunction in cancer and viral infection. Nature Reviews Immunology 2025, 1-18. PMID: 40216888, DOI: 10.1038/s41577-025-01161-6.Peer-Reviewed Original ResearchChronic viral infectionsCD8+ T cellsViral infectionT cellsCD8+ T cell dysfunctionT cell dysfunctionClinical management of cancerChronically infected cellsManagement of cancerAntigenic stimulationClinical managementHypofunctional stateTherapeutic strategiesInfectionCancerInfected cellsCell deathPathological scenariosPrevent exhaustionCD8AnergyCellsNeoplasmsHypofunctionDysfunctionMechanisms and strategies for organ recovery
Andrijevic D, Spajic A, Hameed I, Sheth K, Parnia S, Griesemer A, Montgomery R, Sestan N. Mechanisms and strategies for organ recovery. Nature Reviews Bioengineering 2025, 1-16. DOI: 10.1038/s44222-025-00293-7.Peer-Reviewed Original ResearchMechanisms of cellular injuryPerfusion systemHeart-lung machineSecondary cellular damageDecreased ATP productionIntracellular acidosisOrgan transplantationViability of mammalian cellsCirculating perfusateOxygen deliveryBlood supplyCellular injuryBlood flowInjured tissuePerfusionRestore circulationPharmacological compoundsIn vitroCell deathCellular demiseMammalian cellsATP productionResuscitation medicineOrgan recoveryBiological mechanismsCryo-EM structure of the brine shrimp mitochondrial ATP synthase suggests an inactivation mechanism for the ATP synthase leak channel
Kumar A, da Fonseca Rezende e Mello J, Wu Y, Morris D, Mezghani I, Smith E, Rombauts S, Bossier P, Krahn J, Sigworth F, Mnatsakanyan N. Cryo-EM structure of the brine shrimp mitochondrial ATP synthase suggests an inactivation mechanism for the ATP synthase leak channel. Cell Death & Differentiation 2025, 1-18. PMID: 40108410, DOI: 10.1038/s41418-025-01476-w.Peer-Reviewed Original ResearchMitochondrial permeability transition poreATP synthaseMammalian ATP synthaseOpening of mitochondrial permeability transition poreMitochondrial inner membraneMitochondrial ATP synthaseC-terminal regionPermeability transition poreCryo-EM structureCrustacean Artemia franciscanaSingle-particle cryo-electron microscopyCryo-electron microscopyMammalian mitochondriaAccumulate large amountsCa2+-inducedInner membraneLeak channelsOuter membranePermeability transitionTransition poreE subunitCell deathMitochondrial dysfunctionMolecular mechanismsCa2+Adding insult to injury: the spectrum of tubulointerstitial responses in acute kidney injury
Baker M, Cantley L. Adding insult to injury: the spectrum of tubulointerstitial responses in acute kidney injury. Journal Of Clinical Investigation 2025, 135: e188358. PMID: 40091836, PMCID: PMC11910233, DOI: 10.1172/jci188358.Peer-Reviewed Original ResearchConceptsAcute kidney injuryTubular epithelial cellsKidney injuryTubular cellsCases of acute kidney injuryImmune-mediated processPersistence of inflammationBiphasic immune responseChronic kidney diseaseCell deathTubular cell injuryLymphocyte subsetsTubular repairCell cycle arrestOutflow obstructionTEC differentiationPreclinical findingsLymphocytic infiltrationProinflammatory macrophagesKidney diseaseModulate inflammationImmune responseActivated macrophagesMetabolic reprogrammingTubular castsNorovirus co-opts NINJ1 for selective protein secretion
Song J, Zhang L, Moon S, Fang A, Wang G, Gheshm N, Loeb S, Cao P, Wallace J, Alfajaro M, Strine M, Beatty W, Jamieson A, Orchard R, Robinson B, Nice T, Wilen C, Orvedahl A, Reese T, Lee S. Norovirus co-opts NINJ1 for selective protein secretion. Science Advances 2025, 11: eadu7985. PMID: 40020060, PMCID: PMC11870086, DOI: 10.1126/sciadv.adu7985.Peer-Reviewed Original ResearchConceptsPlasma membrane ruptureDamage-associated molecular patternsNS1 secretionNinjurin-1Programmed cell deathAmino acid residuesViral replication sitesViral protein NS1CRISPR screensIntracellular viral proteinsMutagenesis studiesMembrane ruptureProtein NS1Unconventional pathwayCaspase-3Protein secretionViral proteinsReplication sitesCell deathMolecular patternsGenetic ablationNS1Pharmaceutical inhibitionDAMP releaseProteinS-Nitrosylation of CRTC1 in Alzheimer’s disease impairs CREB-dependent gene expression induced by neuronal activity
Zhang X, Vlkolinsky R, Wu C, Dolatabadi N, Scott H, Prikhodko O, Zhang A, Blanco M, Lang N, Piña-Crespo J, Nakamura T, Roberto M, Lipton S. S-Nitrosylation of CRTC1 in Alzheimer’s disease impairs CREB-dependent gene expression induced by neuronal activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2418179122. PMID: 40014571, PMCID: PMC11892585, DOI: 10.1073/pnas.2418179122.Peer-Reviewed Original ResearchConceptsActivity-dependent gene expressionGene expressionAlzheimer's diseaseCREB-dependent gene expressionS-nitrosylationNitric oxide (NO)-related speciesTargets of S-nitrosylationNeuronal activity-dependent gene expressionPathogenesis of ADDecreased neurite lengthIncreased neuronal cell deathNeuronal cell deathSynaptic plasticityTranscriptional pathwaysCell deathCRISPR/Cas9 techniqueTranscription coactivator 1AD modelLong-term memory formationIncreased S-nitrosylationLong-term potentiationTherapeutic targetExpressionNeurite lengthCerebrocortical neurons
2024
Immunogenicity of cell death and cancer immunotherapy with immune checkpoint inhibitors
Catanzaro E, Beltrán-Visiedo M, Galluzzi L, Krysko D. Immunogenicity of cell death and cancer immunotherapy with immune checkpoint inhibitors. Cellular & Molecular Immunology 2024, 22: 24-39. PMID: 39653769, PMCID: PMC11685666, DOI: 10.1038/s41423-024-01245-8.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsImmunogenic cell deathImmunogenic cell death inducerCheckpoint inhibitorsRefractory to immune checkpoint inhibitorsImmunogenicity of cell deathFraction of patientsCombinatorial treatment strategiesAdaptive immune responsesCell deathCombinatorial partnersCancer immunotherapyCombinatorial regimensClinical findingsClinical managementTreatment strategiesClinical activityImmune responseImmunotherapyPatientsCancerOncology settingInhibitorsDeathInducerDevelopment of a small molecule-based two-photon photosensitizer for targeting cancer cells
Lee D, Cao Y, Juvekar V, Sauraj, Noh C, Shin S, Liu Z, Kim H. Development of a small molecule-based two-photon photosensitizer for targeting cancer cells. Journal Of Materials Chemistry B 2024, 12: 12232-12238. PMID: 39469993, DOI: 10.1039/d4tb01706d.Peer-Reviewed Original ResearchConceptsTarget cancer cellsReactive oxygen speciesPhotodynamic therapyCancer cellsDiverse cell linesInduced ROS productionColon cancer tissuesTwo-photon (TPCell deathLow dark toxicityCancer modelsTwo-photon photosensitizerROS productionCancer selectivityInduce cell damageThree-dimensional spheroidsCell linesTP excitationImaging-guided photodynamic therapyCancer tissuesOxygen speciesTP-PDTFerroptosis in Osteoarthritis: Towards Novel Therapeutic Strategy
Zhang Y, Li J, Liu J, Gao Y, Li K, Zhao X, Liu Y, Wang D, Hu X, Wang Z. Ferroptosis in Osteoarthritis: Towards Novel Therapeutic Strategy. Cell Proliferation 2024, 58: e13779. PMID: 39624950, PMCID: PMC11882765, DOI: 10.1111/cpr.13779.Peer-Reviewed Original ResearchArticular cartilageTherapeutic strategiesChondrocyte viabilityCell deathMechanical stressNovel therapeutic strategiesOA cartilagePotential therapeutic strategyIron-dependent formPersistent painRegulated cell deathAutophagic cell deathIron overloadPathogenetic mechanismsExtracellular matrix integrityInflammatory responseIdentification of High-Efficiency β-Catenin Protein Degradation As Critical Vulnerability in B-Cell Malignancies
Cosgun K, Robinson M, Agadzhanian N, Cheng Z, Oulghazi S, Berning P, Fonseca-Arce D, Kume K, Fontaine J, Chan L, Lee J, Yu F, Qian Z, Song J, Chan W, Chen J, Taketo M, Schjerven H, Müschen M. Identification of High-Efficiency β-Catenin Protein Degradation As Critical Vulnerability in B-Cell Malignancies. Blood 2024, 144: 4125-4125. DOI: 10.1182/blood-2024-208125.Peer-Reviewed Original ResearchProtein degradation pathwaysB-ALL cellsProtein degradationRepression of MYCTranscriptional activity of MYCCell deathAcute cell deathLoss of colony formationChIP-seq analysisActive enhancer marksB-cell malignanciesSuper-enhancer regionsActivation of MYCIkaros transcription factorB-lymphoid cellsCell linesB cell identityDefective protein degradationB-cateninNon-lymphoid cell linesDegradation pathwayMantle cell lymphomaProtein levelsB-ALLChIP-seqTargeting β-Catenin Protein Degradation in Refractory B-Cell Malignancies
Cosgun K, Robinson M, Agadzhanian N, Berning P, Fonseca-Arce D, Leveille E, Kothari S, Davids M, Jellusova J, Müschen M. Targeting β-Catenin Protein Degradation in Refractory B-Cell Malignancies. Blood 2024, 144: 1412. DOI: 10.1182/blood-2024-208598.Peer-Reviewed Original ResearchProtein degradationRepression of MYCTranscriptional repression of MYCTranscriptional repressionPromote survivalProteasome inhibitorsProtein degradation pathwaysCell typesN-terminal residuesInduce cell deathRefractory B-cell malignanciesB-cateninB-cell malignanciesRNAi screenInteractome studiesB cell selectionRepressive complexesGene dependenciesProteasomal degradationB cellsChemogenomic screensProteasome inhibitor bortezomibActivated mycDeletion of Ctnnb1Cell deathMetabolic Determinants of Ferroptosis in B-Cell Lymphoma
Leveille E, Bramson E, Robinson M, Bertomeu T, Chatr-Aryamontri A, Kothari S, Müschen M. Metabolic Determinants of Ferroptosis in B-Cell Lymphoma. Blood 2024, 144: 976-976. DOI: 10.1182/blood-2024-209077.Peer-Reviewed Original ResearchB-cell lymphomaB-cell malignanciesB cellsSensitivity to ferroptosisLipid membrane remodelingFerroptosis inducersMyeloid leukemiaSolid tumorsMembrane remodelingCRISPR screensGene dependenciesAssociated with significantly worse survivalTreatment of B-cell lymphomaB-cell lymphoma modelElimination of B cellsPUFA metabolismCysteine-glutamate antiporterCell deathMature splenic B cellsTherapy-resistant tumorsNon-apoptotic form of cell deathAnalysis of clinical dataDominant-negative p53Vulnerability to ferroptosisWhole-genome CRISPR screenPARG inhibition induces nuclear aggregation of PARylated PARP1
Paradkar S, Purcell J, Cui A, Friedman S, Noronha K, Murray M, Sundaram R, Bindra R, Jensen R. PARG inhibition induces nuclear aggregation of PARylated PARP1. Structure 2024, 32: 2083-2093.e5. PMID: 39406247, DOI: 10.1016/j.str.2024.09.006.Peer-Reviewed Original ResearchFlaviviruses manipulate mitochondrial processes to evade the innate immune response
Boytz R, Keita K, Pawlak J, Laurent-Rolle M. Flaviviruses manipulate mitochondrial processes to evade the innate immune response. Npj Viruses 2024, 2: 47. PMID: 39371935, PMCID: PMC11452341, DOI: 10.1038/s44298-024-00057-x.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMitochondrial processesAntiviral signaling proteinProgrammed cell deathRegulate various aspectsInnate immune response to viral infectionEukaryotic organellesResponse to viral infectionMitochondrial biologyInnate immune responseMitochondrial morphologyCellular processesSignaling proteinsCell deathImmune response to viral infectionInnate immunityMitochondriaCalcium homeostasisFlavivirusesViral infectionImmune responseOrganellesPathogensDynamic structureProteinHomeostasisCarrier-free multifunctional nanomedicine for enhanced hyperthermic intraperitoneal chemotherapy against abdominal pelvic tumors
Fang H, Zhang L, Wu Y, Chen L, Deng Z, Zheng Z, Wang Y, Yang Y, Chen Q. Carrier-free multifunctional nanomedicine for enhanced hyperthermic intraperitoneal chemotherapy against abdominal pelvic tumors. Chemical Engineering Journal 2024, 498: 155781. DOI: 10.1016/j.cej.2024.155781.Peer-Reviewed Original ResearchHyperthermic intraperitoneal chemotherapyImmunogenic cell deathDamage-associated molecular patternsPelvic tumorsIntraperitoneal chemotherapyGambogic acidAnti-tumor immune response in vivoInfiltration of cytotoxic T lymphocytesTriggering immunogenic cell deathRelease of damage-associated molecular patternsCancer cellsImmune responses in vivoCytotoxic T lymphocytesInduce apoptosis of cancer cellsApoptosis of cancer cellsResponses in vivoInhibitor of heat shock proteinCell deathHyperthermia-induced cell deathPenetration of nanoparticlesTumor extracellular matrixHeat shock proteinsOvarian cancerTumor microenvironmentT lymphocytes
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