2025
Cellular pan-chain acyl-CoA profiling reveals SLC25A42/SLC25A16 in mitochondrial CoA import and metabolism
Liu R, Zhang Z, Kyaw A, Grabińska K, Shah H, Shen H. Cellular pan-chain acyl-CoA profiling reveals SLC25A42/SLC25A16 in mitochondrial CoA import and metabolism. Nature Metabolism 2025, 7: 1871-1888. PMID: 40925986, PMCID: PMC12460162, DOI: 10.1038/s42255-025-01358-y.Peer-Reviewed Original ResearchConceptsAcyl-CoAMitochondrial acyl-CoACoA-dependent pathwayAcyl-CoA profileCultured human cellsMitochondrial importCoA-dependentCoA poolTCA cycleFatty acid oxidationSpatial regulationSubcellular compartmentsCoA biosynthesisCoA metabolismLipid anabolismCoenzyme ACellular metabolismCatabolic processHuman cellsInborn errorsCoASHImportant processesThioester derivativesAcid oxidationMetabolismCurrent Advances in Anticancer Properties of Heptamethine Carbocyanine DZ‐1 Conjugated to Artesunate: Generation of Reactive Oxygen Species
Narayanasamy B, Helmueller S, Zhang Y, Lee Y. Current Advances in Anticancer Properties of Heptamethine Carbocyanine DZ‐1 Conjugated to Artesunate: Generation of Reactive Oxygen Species. Journal Of Cellular Biochemistry 2025, 126: e70062. PMID: 40891511, DOI: 10.1002/jcb.70062.Peer-Reviewed Original ResearchConceptsCancer cellsMechanism of actionGeneration of reactive oxygen speciesReactive oxygen speciesN-acetyl cysteine treatmentKilling of cancer cellsCell linesDUTP nick end labeling assayDose-dependent cytotoxic activityNick end labeling assayTransferase dUTP nick end labeling assayBax-deficient HCT116 cellsTerminal deoxynucleotidyl transferase dUTP nick end labeling assayDeoxynucleotidyl transferase dUTP nick end labeling assayCell survival assayOVCAR-3 cell lineMitochondrial outer membrane potentialTreated cancer cellsInvolvement of apoptosisSuppression of ROS generationWild-type cellsOuter membrane potentialCancer cell linesAnticancer propertiesJC-1 assayCYP1B1-AS1 regulates CYP1B1 to promote Coxiella burnetii pathogenesis by inhibiting ROS and host cell death
Arunima A, Niyakan S, Butler S, Clark S, Pinson A, Kwak D, Case E, Qian X, de Figueiredo P, van Schaik E, Samuel J. CYP1B1-AS1 regulates CYP1B1 to promote Coxiella burnetii pathogenesis by inhibiting ROS and host cell death. Nature Communications 2025, 16: 7493. PMID: 40796858, PMCID: PMC12344041, DOI: 10.1038/s41467-025-62762-2.Peer-Reviewed Original ResearchConceptsMitochondrial homeostasisTranscriptome analysisRegulation of mitochondrial homeostasisHost cell deathAnti-pathogen responsesCausative agentNuclear translocation assayAgent of Q feverBidirectional promoterNon-coding RNAsCausative agent of Q feverCo-regulationTranslocation assayCore setLncRNA researchLong non-coding RNAsCell deathPromoter assayMitochondrial dysfunctionIntracellular environmentSpatiotemporal mannerHost macrophagesRegulation of inflammationTHP-1 macrophagesAhR signaling2-hydroxyglutarate mediates whitening of brown adipocytes coupled to nuclear softening upon mitochondrial dysfunction
Kaul H, Isermann L, Senft K, Popovic M, Georgomanolis T, Baumann L, Sivanesan P, Pouikli A, Nolte H, Lucic B, Hildebrandt X, Seidel K, Gnad T, Gaedke F, Göbel U, Peters F, Cherevatenko M, Park J, Schauss A, Peltzer N, Brüning J, Kornfeld J, Pfeifer A, Langer T, Lusic M, Wickström S, Frezza C, Trifunovic A. 2-hydroxyglutarate mediates whitening of brown adipocytes coupled to nuclear softening upon mitochondrial dysfunction. Nature Metabolism 2025, 7: 1593-1613. PMID: 40750944, PMCID: PMC12373511, DOI: 10.1038/s42255-025-01332-8.Peer-Reviewed Original ResearchConceptsBrown adipose tissueNuclear stiffnessResponse to mitochondrial dysfunctionMitochondrial dysfunctionLipid droplet enlargementD-2HGAccumulation of lipid dropletsProtease ClpPFatty acid oxidationBrown adipocytesCellular homeostasisEpigenetic signaturesCellular metabolismGene expressionOncometabolite D-2-hydroxyglutarateD-2-hydroxyglutarateLipid dropletsMolecular underpinningsLipid accumulationExtrinsic cuesNuclear softeningAcid oxidationAdipose tissueClpPMitochondriaUCP2 mediates mitochondrial dynamics to induce AgRP neuronal activity
Jin S, Yoon N, Liu Z, Menale C, Kim J, Diano N, Diano S. UCP2 mediates mitochondrial dynamics to induce AgRP neuronal activity. Molecular Metabolism 2025, 99: 102215. PMID: 40683468, PMCID: PMC12328681, DOI: 10.1016/j.molmet.2025.102215.Peer-Reviewed Original ResearchConceptsDynamin-related protein 1Mitochondrial dynamicsAgRP neuron activityExpression level of uncoupling protein 2AgRP neuronsFeeding behaviorWhole-body energy homeostasisLevel of uncoupling protein 2AgRP neuronal functionMitochondrial fatty acid utilizationMRNA expression levelsWhole-body energy metabolismMitochondrial proteinsMitochondrial fissionMitochondrial morphologyFatty acid oxidationAgouti-related protein (AgRP)-expressing neuronsNeuronal activityFatty acid utilizationHypothalamic AgRP neuronsAcid utilizationEnergy homeostasisUCP2Fasting-induced food intakeEnergy metabolismGlycogen supports glycolytic plasticity in neurons
Singh M, Wolfe A, Vishwanath A, Tsives A, Gonzalez I, Emerson S, Goodman R, Colón-Ramos D. Glycogen supports glycolytic plasticity in neurons. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2509003122. PMID: 40638090, PMCID: PMC12280961, DOI: 10.1073/pnas.2509003122.Peer-Reviewed Original ResearchConceptsCaenorhabditis elegans</i>Conditions of mitochondrial dysfunctionCells of living animalsSynaptic vesicle recyclingTransient hypoxiaSingle cellsVesicle recyclingRNAi screenAssociated with defectsMitochondrial functionResponse to activationGlycolytic stateMitochondrial dysfunctionEnergy metabolism in vivoMetabolism in vivoSynaptic functionNeuronsIn vivoHypoxiaEnergy reservesGlycogen phosphorylaseGlycogenOrthologsCaenorhabditisMutantsmtDNA transfer from senescent cancer cells to MDSCs promotes immunosuppression
Cañadas I, Murayama T, Galluzzi L. mtDNA transfer from senescent cancer cells to MDSCs promotes immunosuppression. Trends In Cancer 2025, 11: 716-718. PMID: 40610348, DOI: 10.1016/j.trecan.2025.06.010.Peer-Reviewed Original ResearchMitofusin 2 controls mitochondrial and synaptic dynamics of suprachiasmatic VIP neurons and related circadian rhythms
Stoiljkovic M, Song J, Hong H, Endle H, Varela L, Catarino J, Gao X, Liu Z, Sotonyi P, Diano S, Cedernaes J, Bass J, Horvath T. Mitofusin 2 controls mitochondrial and synaptic dynamics of suprachiasmatic VIP neurons and related circadian rhythms. Journal Of Clinical Investigation 2025, 135: e185000. PMID: 40590229, PMCID: PMC12208536, DOI: 10.1172/jci185000.Peer-Reviewed Original ResearchConceptsMitochondrial dynamicsMitofusin 2Perturb mitochondrial dynamicsDaily biological rhythmsEnvironmental cuesCellular adaptationMammalian organismsCircadian oscillatorVIP neuronsConditional ablationMitochondriaLD cycleCircadian rhythmicityLight/darkAdvanced phase angleCircadian rhythmSynaptic input organizationMitofusinBiological rhythmsMfn2OrganizationInput organizationNeuronsCore body temperatureSynaptic dynamicsTriglycerides are an important fuel reserve for synapse function in the brain
Kumar M, Wu Y, Knapp J, Pontius C, Park D, Witte R, McAllister R, Gupta K, Rajagopalan K, De Camilli P, Ryan T. Triglycerides are an important fuel reserve for synapse function in the brain. Nature Metabolism 2025, 7: 1392-1403. PMID: 40595405, PMCID: PMC12286841, DOI: 10.1038/s42255-025-01321-x.Peer-Reviewed Original ResearchConceptsLipid dropletsFatty acidsMitochondrial ATP productionFunction in vivoActivity-dependent fashionNerve terminalsATP productionNeuronal function in vivoSynapse functionAdult male miceTriglyceride lipaseIn vivo neuronsDDHD2Neuronal bioenergeticsMale miceAcute blockElectrical silenceMetabolic supportNeuronsNerveFuel reservesElectrical activityMitochondriaCognitive functionBioenergeticsMitochondrial complex IV remodeling in tumor-associated macrophages amplifies interferon signaling and promotes anti-tumor immunity
Clark M, Simeonov K, Mowel W, Michieletto M, Joannas L, Wright J, Erickson I, Johnson L, Krishnan R, de la Fuente-Núñez C, Minn A, Henao-Mejia J. Mitochondrial complex IV remodeling in tumor-associated macrophages amplifies interferon signaling and promotes anti-tumor immunity. Immunity 2025, 58: 1670-1687.e12. PMID: 40592341, PMCID: PMC12259027, DOI: 10.1016/j.immuni.2025.06.006.Peer-Reviewed Original ResearchConceptsImmune checkpoint blockadeTumor-associated macrophagesAnti-tumor immunityB16 melanoma tumor growthICB responseImmune checkpoint blockade efficacyPro-tumoral tumor-associated macrophagesTumor-associated macrophage functionMelanoma tumor growthCheckpoint blockadeTumor progressionTumor growthSTING activationInterferon SignalingMitochondrial DNA releaseRNA-based therapeuticsTranscriptional programsInterferonFunctional adaptationMacrophagesDNA releaseComplex IV subunitsEfficacyImmunityElectron transport chainNovel Variants in VARS2 Demonstrate the Phenotypic Variability of a Rare Mitochondriopathy That Responds to Valine Supplementation
Marquez J, Viviano S, Rahman F, Strohbehn S, Allworth A, Perez N, Research U, Network U, Saneto R, Anna S, Portmann M, Blue E, Glass I, Deniz E, Shelkowitz E. Novel Variants in VARS2 Demonstrate the Phenotypic Variability of a Rare Mitochondriopathy That Responds to Valine Supplementation. Journal Of Inherited Metabolic Disease 2025, 48: e70053. PMID: 40563223, PMCID: PMC12303584, DOI: 10.1002/jimd.70053.Peer-Reviewed Original ResearchConceptsMitochondrial aminoacyl-tRNA synthetasesCognate tRNA moleculesPhenotypic variabilityAminoacyl-tRNA synthetasesXenopus modelBi-allelic variantsMitochondrial proteinsTRNA moleculesDiverse groupMitochondrial machineryLoss of functionNovel variantsResidual enzyme activityVARS2Mitochondrial functionMitochondrial encephalopathyValine supplementationEnzyme activityClinical phenotypeMitochondriopathyGenesVariantsModels of diseaseAxial hypotoniaAmino acid supplementationUpdate of the sideroflexin (SLC56) gene family
Katsafadou A, Nebert D, Krupenko S, Thompson D, Vasiliou V. Update of the sideroflexin (SLC56) gene family. Human Genomics 2025, 19: 69. PMID: 40542427, PMCID: PMC12180156, DOI: 10.1186/s40246-025-00779-w.Peer-Reviewed Original ResearchConceptsIron-sulfur cluster assemblyMitochondrial iron-regulatedMitochondrial iron homeostasisMitochondrial serine transporterMitochondrial transmembrane proteinOxidative phosphorylation disordersSolute carrier familyEukaryotic speciesOne-carbon metabolismMitochondrial researchGene familyModel organismsCellular homeostasisEvolutionary trajectoriesMitochondrial metabolismTransmembrane domainCongenital sideroblastic anemiaTransmembrane proteinsCarrier familySideroflexinHeme biosynthesisIron regulationCitrate metabolismMitochondrial functionSerine transportReduced DJ-1-F1Fo ATP synthase association correlates with midbrain dopaminergic neuron vulnerability in idiopathic Parkinson’s disease
Abulimiti A, Bae H, Ali A, Balakrishnan S, Tsujishita M, Gveric D, Tierney T, Jonas E, Smith P, Gentleman S, Alavian K. Reduced DJ-1-F1Fo ATP synthase association correlates with midbrain dopaminergic neuron vulnerability in idiopathic Parkinson’s disease. Science Advances 2025, 11: eads3051. PMID: 40479058, PMCID: PMC12143374, DOI: 10.1126/sciadv.ads3051.Peer-Reviewed Original ResearchConceptsProximity ligation assayVentral tegmental areaF1Fo-ATP synthaseProximity ligation assay signalsMetabolic efficiencyVentral tegmental area neuronsMitochondrial metabolic efficiencyProtein productionLigation assayMitochondrial activityMetabolic homeostasisIntracellular compartmentsMitochondrial efficiencyDistal neuritesParkinson's diseaseControl postmortem brainsImpaired mitochondrial efficiencySubstantia nigra pars compactaDopaminergic neuron vulnerabilityMesDA neuronsMesencephalic dopaminergicNeuronal vulnerabilityTegmental areaNeuronal subpopulationsIdiopathic Parkinson's diseaseA robust multiplex-DIA workflow profiles protein turnover regulations associated with cisplatin resistance and aneuploidy
Salovska B, Li W, Bernhardt O, Germain P, Wang Q, Gandhi T, Reiter L, Liu Y. A robust multiplex-DIA workflow profiles protein turnover regulations associated with cisplatin resistance and aneuploidy. Nature Communications 2025, 16: 5034. PMID: 40447611, PMCID: PMC12125295, DOI: 10.1038/s41467-025-60319-x.Peer-Reviewed Original ResearchConceptsMS platformsMass spectrometryDrug discoveryCisplatin resistanceDegradation kineticsDegradation profileAssociated with cisplatin resistanceProtein turnoverLabeled channelsProtein complex subunitsRespiratory complex IMitochondrial metabolic adaptationRobust workflowProtein degradation profilesCancer cell modelsMeasure protein turnoverProtein turnover regulationProteome dynamicsSpectrometryHigh-throughputComplex ICellular processesComplex subunitsSILAC labelingAneuploid genomesPartial mitochondrial involvement in the antiproliferative and immunostimulatory effects of PT-112
Soler-Agesta R, Beltrán-Visiedo M, Sato A, Yamazaki T, Guilbaud E, Yim C, Congenie M, Ames T, Anel A, Galluzzi L. Partial mitochondrial involvement in the antiproliferative and immunostimulatory effects of PT-112. OncoImmunology 2025, 14: 2507245. PMID: 40386940, PMCID: PMC12091903, DOI: 10.1080/2162402x.2025.2507245.Peer-Reviewed Original ResearchConceptsImmunogenic cell deathTS/A cellsPD-L1Immune checkpoint inhibitorsExposure of calreticulinLigand PD-L1Type I IFN secretionSecrete type I IFNsRelease of HMGB1MHC class IMHC class I moleculesClass I moleculesType I IFNImmunostimulatory signalsCheckpoint inhibitorsCell surfaceTreatment discontinuationClinical responsePreclinical modelsMalignant cellsSolid tumorsTumor typesColorectal carcinomaGenetic alterationsHMGB1 releaseSARM1 loss protects retinal ganglion cells in a mouse model of Autosomal Dominant Optic Atrophy
Ding C, Ndiaye P, Campbell S, Fry M, Gong J, Wienbar S, Gibbs W, Morquette P, Chao L, H. M, Schwarz T. SARM1 loss protects retinal ganglion cells in a mouse model of Autosomal Dominant Optic Atrophy. Journal Of Clinical Investigation 2025, 135: e191315. PMID: 40344041, PMCID: PMC12165793, DOI: 10.1172/jci191315.Peer-Reviewed Original ResearchConceptsAutosomal dominant optic atrophyRetinal ganglion cellsOptic atrophy type 1Dominant optic atrophyOptic atrophyMouse modelRGC degenerationGanglion cellsOptic nerve degenerationHereditary optic neuropathyMitochondrial intermembrane spaceRGC lossOptic neuropathyRGC functionVision lossNerve degenerationIntermembrane spaceType 1Mitochondrial fragmentationDegeneration phenotypeMitochondrial defectsTherapeutic targetMembrane dynamicsMiceTIR motifMitochondrial gene SLC25A24 regulated anti-tumor immunity and inhibited the proliferation and metastasis of colorectal cancer by PKG1-dependent cGMP/PKG1 pathway
Gao Y, Peng Y, Zhou Y, Zhu J, Fu S, Chen Y, Cai C, Han Y, Shen H, Zeng S, Mao L, Xiao Z. Mitochondrial gene SLC25A24 regulated anti-tumor immunity and inhibited the proliferation and metastasis of colorectal cancer by PKG1-dependent cGMP/PKG1 pathway. International Immunopharmacology 2025, 157: 114664. PMID: 40334626, DOI: 10.1016/j.intimp.2025.114664.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsAnti-tumor immunityColorectal cancerResponse to immune checkpoint inhibitorsAssociated with worse overall survivalKaplan-Meier survival analysisProgression-free survivalTumor immune regulationMetastasis of colorectal cancerMitochondrial solute carriersMicrosatellite instabilityColorectal cancer cell linesColorectal cancer patientsCancer-related mortalityProliferation-related markersCheckpoint inhibitorsColorectal cancer progressionOverall survivalImmune infiltrationPotential therapeutic targetPrognostic markerUnfavorable prognosisColorectal cancer tissuesImmune regulationClinical cohortMitochondrial fatty acid synthesis and MECR regulate CD4+ T cell function and oxidative metabolism
Steiner K, Young A, Patterson A, Sugiura A, Watson M, Preston S, Zhelonkin A, Jennings E, Chi C, Heintzman D, Pahnke A, Toudji Y, Hatem Z, Madden M, Arner E, Sewell A, Blount A, Okparaugo R, Fallman E, Krystofiak E, Sheldon R, Gibson-Corley K, Voss K, Nowinski S, Jones R, Mogilenko D, Rathmell J. Mitochondrial fatty acid synthesis and MECR regulate CD4+ T cell function and oxidative metabolism. The Journal Of Immunology 2025, 214: 958-976. PMID: 40204636, PMCID: PMC12123211, DOI: 10.1093/jimmun/vkaf034.Peer-Reviewed Original ResearchConceptsT cell subsetsCD4+ T cell subsetsMitochondrial fatty acid synthesisT cell functionT cellsFatty acid synthesisDecreased mitochondrial respirationTricarboxylic acid intermediatesLipid metabolism genesT cell fateSensitivity to ferroptosisIncreased cell deathCD4+ T cell functionCD8+ T cell numbersCD4+ T cell proliferationMitochondrial stressMetabolic genesCD4+ T cellsCRISPR/Cas9 screenMitochondrial respirationModel of inflammatory bowel diseaseAcid synthesisFitness disadvantageMemory T cellsT cell numbersMitochondrial tRNA fragment, mt-tRF-Tyr-GTA-001 (tRF-21-X3OJI8EWB), in breast cancer and its potential clinical implications
Wang J, Katsaros D, Wang Z, Ma L, Casetta E, Fei P, Denti P, Grimaudo I, Chen S, Deng Y, Yu H. Mitochondrial tRNA fragment, mt-tRF-Tyr-GTA-001 (tRF-21-X3OJI8EWB), in breast cancer and its potential clinical implications. Breast Cancer Research And Treatment 2025, 211: 675-685. PMID: 40102335, DOI: 10.1007/s10549-025-07682-x.Peer-Reviewed Original ResearchConceptsBreast tumorsInvolvement of tRNARegulation of cell phenotypeSuppress breast cancer progressionSmall non-coding RNAsIn silico analysisOncogenic transcription factorHormone receptor statusCox proportional hazards regressionMitochondrial tRNAsBreast cancer progressionCleaves tRNATRNA fragmentsProportional hazards regressionRNase 4Non-coding RNAsPotential clinical implicationsResting mast cellsTranscription factorsSilico analysisReceptor statusTumor immunityQuantitative RT-PCRTRNATumor gradep53 enhances DNA repair and suppresses cytoplasmic chromatin fragments and inflammation in senescent cells
Miller K, Li B, Pierce-Hoffman H, Patel S, Lei X, Rajesh A, Teneche M, Havas A, Gandhi A, Macip C, Lyu J, Victorelli S, Woo S, Lagnado A, LaPorta M, Liu T, Dasgupta N, Li S, Davis A, Korotkov A, Hultenius E, Gao Z, Altman Y, Porritt R, Garcia G, Mogler C, Seluanov A, Gorbunova V, Kaech S, Tian X, Dou Z, Chen C, Passos J, Adams P. p53 enhances DNA repair and suppresses cytoplasmic chromatin fragments and inflammation in senescent cells. Nature Communications 2025, 16: 2229. PMID: 40044657, PMCID: PMC11882782, DOI: 10.1038/s41467-025-57229-3.Peer-Reviewed Original ResearchConceptsCytoplasmic chromatin fragmentsDNA repairGenome integrityChromatin fragmentsNuclear DNA damage signalsGenomic instabilitySenescent cellsActivation of p53Controlling DNA repairATM-dependent mannerDNA damage signalingSignatures of agingAge-associated accumulationActivate p53P53 activationHallmarks of agingDamage signalingAge-associated diseasesSignaling circuitsP53Molecular circuitsEnhanced DNA repairGenomePharmacological inhibitionAge-associated inflammation
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