Shanshan Liu, PhD
Associate Research Scientist in Cell BiologyCards
About
Research
Publications
2026
SLC33A1 exports oxidized glutathione to maintain endoplasmic reticulum redox homeostasis
Liu S, Gad M, Li C, Cho K, Liu Y, Wangdu K, Belay V, Millet A, Kojima H, Sanford H, Wölk M, Urnavicius L, Fedorova M, Patti G, Vinogradova E, Hite R, Birsoy K. SLC33A1 exports oxidized glutathione to maintain endoplasmic reticulum redox homeostasis. Nature Cell Biology 2026, 28: 903-914. PMID: 41998286, DOI: 10.1038/s41556-026-01922-y.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulumER-associated degradation pathwayRedox homeostasisER redox balanceER redox homeostasisCryogenic electron microscopy structureProtein disulfide isomeraseLiposome-based assayElectron microscopy structureGSSG:GSH ratioRedox-active metabolitesProtein maturationGSSG exportCRISPR screensMammalian cellsDisulfide isomeraseSLC33A1ER stressMembrane proteinsEfficient maturationRedox balanceGSSG accumulationMolecular dynamics simulationsProteinDegradation pathway
2023
Autoregulatory control of mitochondrial glutathione homeostasis
Liu Y, Liu S, Tomar A, Yen F, Unlu G, Ropek N, Weber R, Wang Y, Khan A, Gad M, Peng J, Terzi E, Alwaseem H, Pagano A, Heissel S, Molina H, Allwein B, Kenny T, Possemato R, Zhao L, Hite R, Vinogradova E, Mansy S, Birsoy K. Autoregulatory control of mitochondrial glutathione homeostasis. Science 2023, 382: 820-828. PMID: 37917749, PMCID: PMC11170550, DOI: 10.1126/science.adf4154.Peer-Reviewed Original ResearchConceptsMetabolic homeostasisMitochondrial GSH transportControl of metabolic homeostasisAutoregulatory controlIron-sulfur clustersGSH importBiosynthetic functionsSLC25A39Proteomic analysisRedox metabolitesAbundance of metabolitesGSH transportAFG3L2MitochondriaDepletion of GSHPhysiological conditionsAbundanceHomeostasisGSH uptakeMetabolitesOrganellesCompensatory increaseRegulationAdequate amountsA mitochondrial SCF‐FBXL4 ubiquitin E3 ligase complex degrades BNIP3 and NIX to restrain mitophagy and prevent mitochondrial disease
Cao Y, Zheng J, Wan H, Sun Y, Fu S, Liu S, He B, Cai G, Cao Y, Huang H, Li Q, Ma Y, Chen S, Wang F, Jiang H. A mitochondrial SCF‐FBXL4 ubiquitin E3 ligase complex degrades BNIP3 and NIX to restrain mitophagy and prevent mitochondrial disease. The EMBO Journal 2023, 42: embj2022113033. PMID: 36896912, PMCID: PMC10308365, DOI: 10.15252/embj.2022113033.Peer-Reviewed Original ResearchConceptsUbiquitin E3 ligase complexE3 ligase complexLigase complexHyperactivated mitophagyMitochondrial diseaseIntegral outer membrane proteinsMitochondrial disease genesMitophagy receptor BNIP3Ubiquitin E3 ligaseOuter membrane proteinsQuality control mechanismsBasal mitophagyDisease genesE3 ligaseNIX proteinGenetic screeningMitophagyRegulatory mechanismsSubstrate degradationBNIP3FBXL4Perinatal lethalityPathological implicationsKnockoutProteinChemical inhibition of mitochondrial fission via targeting the DRP1-receptor interaction
Yang J, Chen P, Cao Y, Liu S, Wang W, Li L, Li J, Jiang Z, Ma Y, Chen S, Zheng S, Qi X, Jiang H. Chemical inhibition of mitochondrial fission via targeting the DRP1-receptor interaction. Cell Chemical Biology 2023, 30: 278-294.e11. PMID: 36827981, DOI: 10.1016/j.chembiol.2023.02.002.Peer-Reviewed Original ResearchConceptsMitochondrial division inhibitorMitochondrial fission inhibitorMitochondrial fissionDrp1 recruitment to mitochondriaChemical inhibitionInhibition of mitochondrial fissionRecruitment to mitochondriaFission inhibitorProtein-protein interaction inhibitorsLive-cell imagingGTPase Drp1GTPase activityMitochondrial morphogenesisDivision inhibitorMitochondrial dynamicsMitochondrial fragmentationMitochondrial morphologyDrp1OPA1 mutationsInteraction inhibitorsMitochondrial toxinsCellular characterizationMitochondriaMultiple receptorsFission
2022
Mitochondrial cristae architecture protects against mtDNA release and inflammation
He B, Yu H, Liu S, Wan H, Fu S, Liu S, Yang J, Zhang Z, Huang H, Li Q, Wang F, Jiang Z, Liu Q, Jiang H. Mitochondrial cristae architecture protects against mtDNA release and inflammation. Cell Reports 2022, 41: 111774. PMID: 36476853, DOI: 10.1016/j.celrep.2022.111774.Peer-Reviewed Original ResearchConceptsMitochondrial intermembrane space bridgingCristae architectureMtDNA releaseCristae organizationIFN-I responseMitochondrial cristae architectureMitochondrial contact siteMitochondrial damageCRISPR knockout screenAging-related degenerative diseasesSAM complexAssembly machineryMitochondrial DNAKnockout screenAging-related degenerative disordersProtein complexesContact sitesMtDNAHallmarks of agingCGAS-STING pathwayNull mutationPhospholipid cardiolipinIFN-IType I interferonCristae disorganizationProtocols for analyzing metabolic derangements caused by increased NADH/NAD+ ratio in cell lines and in mice
Liu S, Ma Y, Jiang H. Protocols for analyzing metabolic derangements caused by increased NADH/NAD+ ratio in cell lines and in mice. STAR Protocols 2022, 3: 101120. PMID: 35106502, PMCID: PMC8784396, DOI: 10.1016/j.xpro.2021.101120.Peer-Reviewed Original ResearchIdentification and characterization of novel MPC1 gene variants causing mitochondrial pyruvate carrier deficiency
Jiang H, Alahmad A, Fu S, Fu X, Liu Z, Han X, Li L, Song T, Xu M, Liu S, Wang J, Albash B, Alaqeel A, Catalina V, Prokisch H, Taylor R, McFarland R, Fang F. Identification and characterization of novel MPC1 gene variants causing mitochondrial pyruvate carrier deficiency. Journal Of Inherited Metabolic Disease 2022, 45: 264-277. PMID: 34873722, DOI: 10.1002/jimd.12462.Peer-Reviewed Original ResearchConceptsMPC deficiencyMitochondrial pyruvate carrierMultiple biosynthetic pathwaysHetero-oligomeric complexesLeigh-like syndromeExpression of MPC1Adenosine triphosphate synthesisMutant cDNAsBiosynthetic pathwayMitochondrial adenosine triphosphate synthesisAutosomal recessive diseasePyruvate carrierTransport pyruvatePatient fibroblastsRare autosomal recessive diseaseMitochondrial respirationTriphosphate synthesisMPC1Primary fibroblastsGene variantsMetabolic moleculesPyruvateOxygen consumption rateRecessive diseaseFunctional analysis
2021
Multifaceted roles of mitochondrial stress responses under ETC dysfunction – repair, destruction and pathogenesis
Liu S, Liu S, Jiang H. Multifaceted roles of mitochondrial stress responses under ETC dysfunction – repair, destruction and pathogenesis. The FEBS Journal 2021, 289: 6994-7013. PMID: 34918460, DOI: 10.1111/febs.16323.Peer-Reviewed Original ResearchConceptsMitochondrial stress responseC. elegans responseMitochondrial diseaseStress responseDamaged mitochondriaMitochondrial stress response pathwaysMitochondrial unfolded protein responsePINK1-Parkin mitophagy pathwayTriggers of stress responsesSignaling mechanismsUnfolded protein responseMitochondrial matrix acidificationStress response pathwaysMitochondrial membrane potentialSevere cellular stressMultifaceted rolesMutant mtDNAMitochondrial disease progressionPINK1-ParkinProteostatic stressC. elegansCaenorhabditis elegansReprogrammed metabolismContext-dependentProtein responseGlycerol-3-phosphate biosynthesis regenerates cytosolic NAD+ to alleviate mitochondrial disease
Liu S, Fu S, Wang G, Cao Y, Li L, Li X, Yang J, Li N, Shan Y, Cao Y, Ma Y, Dong M, Liu Q, Jiang H. Glycerol-3-phosphate biosynthesis regenerates cytosolic NAD+ to alleviate mitochondrial disease. Cell Metabolism 2021, 33: 1974-1987.e9. PMID: 34270929, DOI: 10.1016/j.cmet.2021.06.013.Peer-Reviewed Original ResearchConceptsGlycerol-3-phosphateLifespan of C. elegansGrowth of cancer cellsComplex I inhibitionGro3PMitochondrial complex I inhibitionMitochondrial diseaseYeast proliferationShuttle activityNADH accumulationBioinformatics analysisNdufs4-/- miceRedox homeostasisSynthesis enzymesBiosynthesisCytosolic NAD+Cancer cellsMouse liverTherapeutic targetMouse brainCellsYeastEvolutionarilyMiceElegansOXPHOS deficiency activates global adaptation pathways to maintain mitochondrial membrane potential
Liu S, Liu S, He B, Li L, Li L, Wang J, Cai T, Chen S, Jiang H. OXPHOS deficiency activates global adaptation pathways to maintain mitochondrial membrane potential. EMBO Reports 2021, 22: embr202051606. PMID: 33655635, PMCID: PMC8025004, DOI: 10.15252/embr.202051606.Peer-Reviewed Original ResearchConceptsMitochondrial membrane potentialIron-sulfur clustersIron-sulfur cluster biosynthesisReduction of mitochondrial membrane potentialRepression of ribosome biogenesisTranscriptional upregulationOxidative phosphorylation mutantsImport receptor Mia40Function of mitochondriaMitochondrial ATP hydrolysisMembrane potentialUpregulation of glycolysisActive stress responseMitochondrial proteomeAdaptive responseRibosome biogenesisCytoplasmic chaperonesRewired metabolismPhosphorylation mutantsOXPHOS deficiencyPrecursor proteinDepolarized mitochondriaOXPHOS subunitsMitochondrial biogenesisATP hydrolysis