Adjunct Faculty
Adjunct faculty typically have an academic or research appointment at another institution and contribute or collaborate with one or more School of Medicine faculty members or programs.
Adjunct rank detailsNelli Mnatsakanyan, PhD
Assistant Professor AdjunctDownloadHi-Res Photo
About
Copy Link
Titles
Assistant Professor Adjunct
Biography
Dr. Mnatsakanyan is currently an Associate Professor at the Pennsylvania State University College of Medicine. She obtained her Ph.D. from Yerevan State University and performed her postdoctoral work at Texas Tech University Health Sciences Center. As a postdoctoral fellow, she studied the catalytic mechanism of the ATP synthase and characterized an important structural unit, beta DELSEED loop region of the ATP synthase that couples ATP synthesis with subunit rotation. Dr. Mnatsakanyan's current research focuses on understanding the molecular mechanism and regulation of the enigmatic cell death channel located in the mitochondrial ATP synthase and its role in mitochondrial permeability transition (mPTP). The goals in her lab are threefold: 1) Identify and structurally characterize the molecular components of mPTP by using cryo-electron microscopy and cryo-electron tomography. 2) Functionally characterize the ATP synthase leak channel and its regulation by using electrophysiology techniques, patch-clamp and planar lipid bilayer recordings. 3) Generate CRISPR/Cas9-edited mice with a low probability of ATP synthase leak channel/mPTP opening and introduce these mutations in transgenic Alzheimer's disease (AD) mice to study if they will protect the mice from the onset of AD-like features. These studies may lead to the structure-based drug design of specific therapeutic compounds for the treatment of mPTP-related neurodegenerative disorders, aging and cancer.
Last Updated on February 13, 2023.
Appointments
Endocrinology
Associate Professor AdjunctPrimary
Other Departments & Organizations
Education & Training
- PhD
- Yerevan State University, Biophysics (2003)
- MS
- Yerevan State University (1999)
- BS
- Yerevan State University (1999)
Research
Copy Link
Overview
Medical Research Interests
alpha7 Nicotinic Acetylcholine Receptor; Alzheimer Disease; Apoptosis; ATP Synthetase Complexes; Mitochondria; Neurodegenerative Diseases; Synaptic Transmission
ORCID
0000-0001-5363-7409
Research at a Glance
Yale Co-Authors
Frequent collaborators of Nelli Mnatsakanyan's published research.
Publications Timeline
A big-picture view of Nelli Mnatsakanyan's research output by year.
Research Interests
Research topics Nelli Mnatsakanyan is interested in exploring.
Elizabeth Jonas, MD
Jing Wu
Pawel Licznerski, PhD
Marc C Llaguno, PhD
26Publications
1,169Citations
Mitochondria
ATP Synthetase Complexes
Neurodegenerative Diseases
alpha7 Nicotinic Acetylcholine Receptor
Publications
2026
Investigation of mitochondrial inner membrane ion conductance by planar lipid bilayer electrophysiology
Kumar A, Margulis E, Mnatsakanyan N. Investigation of mitochondrial inner membrane ion conductance by planar lipid bilayer electrophysiology. Frontiers In Physiology 2026, 17: 1782998. PMID: 42088950, PMCID: PMC13137367, DOI: 10.3389/fphys.2026.1782998.Peer-Reviewed Original ResearchAltmetricConceptsInner membrane vesiclesMitochondrial ion channelsBiophysical characterizationPlanar lipid bilayer electrophysiologyOuter mitochondrial membraneNormal mitochondrial functionMitochondrial proteinsMitochondrial membraneCellular processesATP synthaseMitochondrial functionCell deathPhysiologically relevant conditionsMetabolic functionsMembrane vesiclesCalcium signalingRegulate ion fluxesIon channelsProteinPathological processesElectrophysiological analysisMembraneIon channel conductanceATPVesiclesReversible dissociation of mitochondrial Complex V balances anabolic and energy-generating needs in cancer
Wang H, Lu J, Henchy C, Mullett S, Richert A, Goetzman E, Toksoz A, Hale L, Wang B, Mnatsakanyan N, Prochownik E. Reversible dissociation of mitochondrial Complex V balances anabolic and energy-generating needs in cancer. IScience 2026, 29: 114889. PMID: 41732272, PMCID: PMC12925242, DOI: 10.1016/j.isci.2026.114889.Peer-Reviewed Original ResearchAltmetricConceptsTCA cycleAnabolic precursorsMitochondrial membrane potentialElectron transport chainMitochondrial complex VDerived cell linesAnaplerotic reactionsEfficient mitochondriaMetabolic re-programmingMT-ATP6Proton poreMitochondrial massComplex VTransport chainATP generationWarburg effectATP accumulationMurine liver cancerReversible dissociationSubstrate productionCell linesATPOxidize glucoseMembrane potentialRe-programming
2025
Early-Stage Alcoholic Cardiomyopathy Highlighted by Metabolic Remodeling, Oxidative Stress, and Cardiac Myosin Dysfunction in Male Rats
Rasicci D, Ge J, Chen A, Wood N, Bodt S, Toro A, Evans A, Golestanian O, Amin S, Pruznak A, Mnatsakanyan N, Silberman Y, Dennis M, Previs M, Lang C, Yengo C. Early-Stage Alcoholic Cardiomyopathy Highlighted by Metabolic Remodeling, Oxidative Stress, and Cardiac Myosin Dysfunction in Male Rats. International Journal Of Molecular Sciences 2025, 26: 6766. PMID: 40725013, PMCID: PMC12296025, DOI: 10.3390/ijms26146766.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsIn vitro motilityAlcoholic cardiomyopathyCardiac myosinMetabolic remodelingATPase activityMitochondrial lipid metabolismMale Sprague-Dawley ratsEthanol-exposed animalsChronic ethanol useSprague-Dawley ratsEthanol-containing dietProteomic approachAlcohol exposureMale ratsMyosinH&E slidesOxidative stress mechanismsIn vitro oxidationEthanol useContractile machineryEarly-stageLipid metabolismCellular aspectsControl groupMyosin dysfunctionCryo-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, 32: 1518-1535. PMID: 40108410, PMCID: PMC12325954, DOI: 10.1038/s41418-025-01476-w.Peer-Reviewed Original ResearchCitationsAltmetricConceptsMitochondrial 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+
2022
Fluid shear stress enhances proliferation of breast cancer cells via downregulation of the c-subunit of the F1FO ATP synthase
Park HA, Brown SR, Jansen J, Dunn T, Scott M, Mnatsakanyan N, Jonas EA, Kim Y. Fluid shear stress enhances proliferation of breast cancer cells via downregulation of the c-subunit of the F1FO ATP synthase. Biochemical And Biophysical Research Communications 2022, 632: 173-180. PMID: 36209586, PMCID: PMC10024463, DOI: 10.1016/j.bbrc.2022.09.084.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsMitochondrial 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 ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsMitochondrial 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
2021
The nucleotide binding affinities of two critical conformations of Escherichia coli ATP synthase
Li Y, Valdez NA, Mnatsakanyan N, Weber J. The nucleotide binding affinities of two critical conformations of Escherichia coli ATP synthase. Archives Of Biochemistry And Biophysics 2021, 707: 108899. PMID: 33991499, PMCID: PMC8278868, DOI: 10.1016/j.abb.2021.108899.Peer-Reviewed Original ResearchCitationsMeSH Keywords and ConceptsConceptsATP synthaseCritical conformationEscherichia coli ATP synthaseRotary catalytic mechanismCatalytic dwell stateCatalytic mechanismAerobic energy metabolismΓ subunitCysteine mutationsTryptophan fluorescenceDwell stateDisulfide bondsEnergetic functionEnergy metabolismCatalytic siteSynthaseCatalytic dwellAffinity changesATPEnzymeAffinityConformationSubunitsMutationsSites
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 ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsFragile 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 leakMaturationMetabolismThe new role of F1Fo ATP synthase in mitochondria-mediated neurodegeneration and neuroprotection
Mnatsakanyan N, Jonas EA. The new role of F1Fo ATP synthase in mitochondria-mediated neurodegeneration and neuroprotection. Experimental Neurology 2020, 332: 113400. PMID: 32653453, PMCID: PMC7877222, DOI: 10.1016/j.expneurol.2020.113400.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsCitationsAltmetricMeSH Keywords and ConceptsConceptsMitochondrial inner membraneATP synthaseInner membraneOxidative phosphorylationF1Fo-ATP synthaseUnique rotational mechanismMitochondrial inner membrane potentialEfficient cellular metabolismInner membrane potentialMitochondrial permeability transition porePermeability transition poreUnique regulatorAbundant proteinsNew roleCellular metabolismCell lifeProton translocationATP synthesisTransition poreCell survivalElectrochemical gradientCertain pathophysiological conditionsSynthaseATPMembrane potentialATP synthase c-subunit ring as the channel of mitochondrial permeability transition: Regulator of metabolism in development and degeneration
Mnatsakanyan N, Jonas EA. ATP synthase c-subunit ring as the channel of mitochondrial permeability transition: Regulator of metabolism in development and degeneration. Journal Of Molecular And Cellular Cardiology 2020, 144: 109-118. PMID: 32461058, PMCID: PMC7877492, DOI: 10.1016/j.yjmcc.2020.05.013.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsMitochondrial permeability transition poreC subunit ringMitochondrial permeability transitionPermeability transitionRegulator of metabolismPermeability transition poreImportant metabolic regulatorMitochondrial megachannelBiology todayRegulatory mechanismsCentral playerTransition poreMetabolic regulatorMolecular compositionRecent findingsRegulatorDegenerative diseasesPathophysiological roleRecent advancesMegachannelRoleMetabolismMysterious phenomenon
Academic Achievements & Community Involvement
Copy Link
Activities
activity "Biomedicine & Pharmacotherapy" Elsevier Journal
2018 - PresentJournal ServiceAssociate EditorDetailsAssociate Editoractivity Society of Neuroscience
09/01/2011 - PresentProfessional OrganizationsMemberDetailsMemberactivity Biophysical Society
09/01/2011 - PresentProfessional OrganizationsMemberDetailsMemberactivity "Bioenergetics, Mitochondria and Metabolism" Subgroup, Biophysical Society
2015 - PresentProfessional OrganizationsMemberDetailsMemberactivity Alzheimer’s Association International Society to Advance Alzheimer’s Research and Treatment (ISTAART)
04/01/2019 - PresentProfessional OrganizationsMemberDetailsMember
Honors
honor RF1 Award
05/15/2021National AwardNational Institute on AgingDetailsUnited Stateshonor Young Bioenergeticist Award
02/19/2018National AwardBiophysical SocietyDetailsUnited Stateshonor K01 Research Scientist Development Award
06/01/2017National AwardNational Institute on AgingDetailsUnited States
Get In Touch
Copy Link