2022
Mitochondrial ATP synthase c-subunit leak channel triggers cell death upon loss of its F1 subcomplex
Mnatsakanyan N, Park HA, Wu J, He X, Llaguno MC, Latta M, Miranda P, Murtishi B, Graham M, Weber J, Levy RJ, Pavlov EV, Jonas EA. Mitochondrial ATP synthase c-subunit leak channel triggers cell death upon loss of its F1 subcomplex. Cell Death & Differentiation 2022, 29: 1874-1887. PMID: 35322203, PMCID: PMC9433415, DOI: 10.1038/s41418-022-00972-7.Peer-Reviewed Original ResearchConceptsMitochondrial permeability transitionATP synthase c-subunitCell deathMitochondrial ATP synthaseChannel activityCellular energy productionLeak channelsVoltage-gated ion channelsF1 subcomplexATP synthaseC subunitInner membraneProkaryotic hostsCell stressPermeability transitionIon channelsGating mechanismOsmotic changesLarge conductanceC-ringChannels triggersNeuronal deathF1SubcomplexOsmotic gradient
2020
ATP Synthase c-Subunit Leak Causes Aberrant Cellular Metabolism in Fragile X Syndrome
Licznerski P, Park HA, Rolyan H, Chen R, Mnatsakanyan N, Miranda P, Graham M, Wu J, Cruz-Reyes N, Mehta N, Sohail S, Salcedo J, Song E, Effman C, Effman S, Brandao L, Xu GN, Braker A, Gribkoff VK, Levy RJ, Jonas EA. ATP Synthase c-Subunit Leak Causes Aberrant Cellular Metabolism in Fragile X Syndrome. Cell 2020, 182: 1170-1185.e9. PMID: 32795412, PMCID: PMC7484101, DOI: 10.1016/j.cell.2020.07.008.Peer-Reviewed Original ResearchConceptsFragile X syndromeC subunitAberrant synaptic developmentHuman fragile X syndromeATP synthase enzymeMental retardation proteinX syndromeATP production efficiencyMRNA translation rateAberrant cellular metabolismATP synthaseMRNA translationTranslation rateCellular metabolismSynaptic growthSynthase enzymeMouse neuronsSynapse maturationSynaptic developmentPharmacological inhibitionLeak channelsSynaptic maturationMembrane leakMaturationMetabolism
2014
An uncoupling channel within the c-subunit ring of the F1FO ATP synthase is the mitochondrial permeability transition pore
Alavian KN, Beutner G, Lazrove E, Sacchetti S, Park HA, Licznerski P, Li H, Nabili P, Hockensmith K, Graham M, Porter GA, Jonas EA. An uncoupling channel within the c-subunit ring of the F1FO ATP synthase is the mitochondrial permeability transition pore. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 10580-10585. PMID: 24979777, PMCID: PMC4115574, DOI: 10.1073/pnas.1401591111.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumCell DeathHEK293 CellsHumansIon Channel GatingIon ChannelsLiposomesMitochondriaMitochondrial Membrane Transport ProteinsMitochondrial MembranesMitochondrial Permeability Transition PoreMutationProtein ConformationProtein SubunitsProton-Translocating ATPasesRatsReactive Oxygen SpeciesConceptsMitochondrial PT poreF1Fo-ATP synthaseATP synthasePermeability transitionCell deathCellular metabolic efficiencyInner mitochondrial membrane permeabilityOxygen species-induced cell deathC subunit ringATP synthase F1Mitochondrial membrane permeabilityMitochondrial permeability transitionC subunitPT poreTight regulationATP productionMolecular identitySingle-channel conductanceChannel closureLeak channelsMPTP openingMetabolic efficiencyMembrane permeabilityHealthy cellsOsmotic shifts
2012
The C-Subunit Ring of the F1FO ATP Synthase Constitutes a Leak Channel that Regulates Cellular Metabolic Efficiency by Counteracting the H+ Translocator
Alavian K, Lazrove E, Nabili P, Li H, Jonas E. The C-Subunit Ring of the F1FO ATP Synthase Constitutes a Leak Channel that Regulates Cellular Metabolic Efficiency by Counteracting the H+ Translocator. Biophysical Journal 2012, 102: 571a. DOI: 10.1016/j.bpj.2011.11.3110.Peer-Reviewed Original Research