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
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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
Assistant Professor AdjunctPrimary
Other Departments & Organizations
- All Institutions
- Endocrinology
- Internal Medicine
Education & Training
- PhD
- Yerevan State University, Biophysics (2003)
- MS
- Yerevan State University (1999)
- BS
- Yerevan State University (1999)
Research
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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
Hilary Blumberg, MD
In-Hyun Park, PhD
36Publications
1,140Citations
Mitochondria
ATP Synthetase Complexes
Neurodegenerative Diseases
alpha7 Nicotinic Acetylcholine Receptor
Publications
2026
Reversible 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-programmingBPS2026 – ATP synthase C-subunit leak channel activity in bipolar disorder
Shen L, Kim J, Kumar A, Mnatsakanyan N, Blumberg H, Park I, Jonas E. BPS2026 – ATP synthase C-subunit leak channel activity in bipolar disorder. Biophysical Journal 2026, 125: 348a. DOI: 10.1016/j.bpj.2025.11.2176.Peer-Reviewed Original ResearchBPS2026 – Mitochondrial resilience mechanisms in Drosophila melanogaster: Structure-function studies of ATP synthase
Betz L, Kumar A, da Fonseca Rezende e Mello J, Mnatsakanyan N. BPS2026 – Mitochondrial resilience mechanisms in Drosophila melanogaster: Structure-function studies of ATP synthase. Biophysical Journal 2026, 125: 306a. DOI: 10.1016/j.bpj.2025.11.1928.Peer-Reviewed Original ResearchBPS2026 – Cryo-EM structure of mammalian ATP synthase bound to the neuroprotective drug dexpramipexole
Wu Y, da Fonseca Rezende e Mello J, Kumar A, Betz L, Palles C, Anang A, Smith E, Mezghani I, Mnatsakanyan N. BPS2026 – Cryo-EM structure of mammalian ATP synthase bound to the neuroprotective drug dexpramipexole. Biophysical Journal 2026, 125: 308a. DOI: 10.1016/j.bpj.2025.11.1938.Peer-Reviewed Original ResearchBPS2026 – Mitochondrial hypermetabolism and dysregulation of ATP synthase leak channel in a humanized APP/PSEN1 Alzheimer’s disease mouse model
Mezghani I, Smith E, Kumar A, Youssef Y, Margulis E, Anang A, Mnatsakanyan N. BPS2026 – Mitochondrial hypermetabolism and dysregulation of ATP synthase leak channel in a humanized APP/PSEN1 Alzheimer’s disease mouse model. Biophysical Journal 2026, 125: 307a. DOI: 10.1016/j.bpj.2025.11.1935.Peer-Reviewed Original Research
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 ResearchAltmetricMeSH 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+BPS2025 - Anti-tuberculosis drug bedaquiline ameliorates calcium-induced mitochondrial permeability transition by inhibiting the ATP synthase leak channel
Kumar A, Smith E, Mezghani I, Eedarapalli S, Wu Y, Amjad E, Park H, Mnatsakanyan N. BPS2025 - Anti-tuberculosis drug bedaquiline ameliorates calcium-induced mitochondrial permeability transition by inhibiting the ATP synthase leak channel. Biophysical Journal 2025, 124: 447a. DOI: 10.1016/j.bpj.2024.11.2381.Peer-Reviewed Original ResearchBPS2025 - The gating mechanism of mitochondrial ATP synthase leak channel
Kumar A, da Fonseca Rezende e Mello J, Wu Y, Betz L, Mezghani I, Smith E, Mnatsakanyan N. BPS2025 - The gating mechanism of mitochondrial ATP synthase leak channel. Biophysical Journal 2025, 124: 449a. DOI: 10.1016/j.bpj.2024.11.2393.Peer-Reviewed Original Research
2024
Mitochondrial ATP synthase as a novel therapeutic drug target in neurodegenerative and ischemic heart diseases
Kumar A, da Fonseca Rezende e Mello J, Wu Y, Mezghani I, Smith E, Mnatsakanyan N. Mitochondrial ATP synthase as a novel therapeutic drug target in neurodegenerative and ischemic heart diseases. Biochimica Et Biophysica Acta (BBA) - Bioenergetics 2024, 1865: 149307. DOI: 10.1016/j.bbabio.2024.149307.Peer-Reviewed Original Research
Academic Achievements & Community Involvement
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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
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