2022
Restricting α-synuclein transport into mitochondria by inhibition of α-synuclein–VDAC complexation as a potential therapeutic target for Parkinson’s disease treatment
Rajendran M, Queralt-Martín M, Gurnev P, Rosencrans W, Rovini A, Jacobs D, Abrantes K, Hoogerheide D, Bezrukov S, Rostovtseva T. Restricting α-synuclein transport into mitochondria by inhibition of α-synuclein–VDAC complexation as a potential therapeutic target for Parkinson’s disease treatment. Cellular And Molecular Life Sciences 2022, 79: 368. PMID: 35718804, PMCID: PMC11072225, DOI: 10.1007/s00018-022-04389-w.Peer-Reviewed Original ResearchMeSH KeywordsAlpha-SynucleinHeLa CellsHumansLipidsMitochondriaParkinson DiseaseVoltage-Dependent Anion ChannelsConceptsVoltage-dependent anion channelVDAC poreProtein-membrane bindingRegulating mitochondrial functionProximity ligation assayInvolvement of alpha-synucleinMembrane bindingMitochondrial respirationMitochondrial functionHeLa cellsLigation assayLipid membranesHexokinase 2MitochondriaTranslocation processComplex inhibitionAnion channelFluorescence correlation spectroscopyAlpha-synucleinMolecular levelMitochondrial toxicityASynTranslocationPeptide therapeuticsTherapeutic target
2020
Tunable Electromechanical Nanopore Trap Reveals Populations of Peripheral Membrane Protein Binding Conformations
Hoogerheide D, Rostovtseva T, Jacobs D, Gurnev P, Bezrukov S. Tunable Electromechanical Nanopore Trap Reveals Populations of Peripheral Membrane Protein Binding Conformations. ACS Nano 2020, 15: 989-1001. PMID: 33369404, PMCID: PMC9019845, DOI: 10.1021/acsnano.0c07672.Peer-Reviewed Original ResearchMeSH KeywordsAlpha-SynucleinMembrane ProteinsMitochondriaMolecular ConformationNanoporesProtein BindingConceptsVoltage-dependent anion channelMembrane surfaceSingle-molecule levelSame membrane surfaceIndividual proteinsAnion channelNeuronal proteinsLipid membranesBinding conformationsLipid surfaceLipid compositionProteinΑ-synucleinMembraneConformationOrders of magnitudeSurfaceUnbindingMitochondriaBindsObserved distributionNanoporesMoleculesΑSynTrapsA lower affinity to cytosolic proteins reveals VDAC3 isoform-specific role in mitochondrial biology
Queralt-Martín M, Bergdoll L, Teijido O, Munshi N, Jacobs D, Kuszak A, Protchenko O, Reina S, Magrì A, De Pinto V, Bezrukov S, Abramson J, Rostovtseva T. A lower affinity to cytosolic proteins reveals VDAC3 isoform-specific role in mitochondrial biology. The Journal Of General Physiology 2020, 152: e201912501. PMID: 31935282, PMCID: PMC7062508, DOI: 10.1085/jgp.201912501.Peer-Reviewed Original ResearchConceptsVoltage-dependent anion channelCysteine residuesMitochondrial outer membraneGeneral molecular mechanismIsoform-specific functionsHigh sequence similarityCysteine-scanning mutagenesisIsoform-specific rolesIsoform-specific regulationUnique functional rolesMitochondrial biologyVDAC isoformsMetabolite exchangeOuter membraneScanning mutagenesisCytosolic proteinsΑ-synucleinAnion channelVoltage-gated channelsMolecular mechanismsMitochondrial bioenergeticsProtein α-synucleinVDAC3VDAC1Functional role
2018
Assessing the role of residue E73 and lipid headgroup charge in VDAC1 voltage gating
Queralt-Martín M, Bergdoll L, Jacobs D, Bezrukov S, Abramson J, Rostovtseva T. Assessing the role of residue E73 and lipid headgroup charge in VDAC1 voltage gating. Biochimica Et Biophysica Acta (BBA) - Bioenergetics 2018, 1860: 22-29. PMID: 30412693, PMCID: PMC8283775, DOI: 10.1016/j.bbabio.2018.11.001.Peer-Reviewed Original ResearchConceptsVoltage-dependent anion channelMitochondrial outer membraneVoltage gatingVoltage-gating processCholesterol binding siteVDAC's roleVDAC functionGating processMetabolite transportOuter membraneAbundant proteinsMOM permeabilityVDAC gatingPlanar lipid membranesAnion channelE73Mitochondrial respirationLipid bilayer systemsLipid headgroup chargeBinding sitesLipid membranesPhospholipid headgroupsElectrophysiology measurementsTransport of ionsRecent studies