The DOI matches its Crossref record; 55 of the 56 references it cites were found in a registry or an index.
Mutant huntingtin directly increases susceptibility of mitochondria to the calcium-induced permeability transition and cytochrome c release
Abstract
Huntington's disease (HD) is initiated by an abnormally expanded polyglutamine stretch in the huntingtin protein, conferring a novel property on the protein that leads to the loss of striatal neurons. Defects in mitochondrial function have been implicated in the pathogenesis of HD. Here, we have examined the hypothesis that the mutant huntingtin protein may directly interact with the mitochondrion and affect its function. In human neuroblastoma cells and clonal striatal cells established from HdhQ7 (wild-type) and HdhQ111 (mutant) homozygote mouse knock-in embryos, huntingtin was present in a purified mitochondrial fraction. Subfractionation of the mitochondria and limited trypsin digestion of the organelle demonstrated that huntingtin was associated with the outer mitochondrial membrane. We further demonstrated that a recombinant truncated mutant huntingtin protein, but not a wild-type, directly induced mitochondrial permeability transition (MPT) pore opening in isolated mouse liver mitochondria, an effect that was prevented completely by cyclosporin A (CSA) and ATP. Importantly, the mutant huntingtin protein significantly decreased the Ca2+ threshold necessary to trigger MPT pore opening. We found a similar increased susceptibility to the calcium-induced MPT in liver mitochondria isolated from a knock-in HD mouse model. The mutant huntingtin protein-induced MPT pore opening was accompanied by a significant release of cytochrome c, an effect completely inhibited by CSA. These findings suggest that the development of specific MPT inhibitors may be an interesting therapeutic avenue to delay the onset of HD.
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“There is evidence from an HD mouse model, and from cultured HD striatal cells (STHdhQ111), that mutant Htt associates directly with the outer mitochondrial membrane49, 57.”
From Mitochondrial Approaches for Neuroprotection (2008) · cites this paper as [57]
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Cites
Green, D. R., & Reed, J. C. (1998) · Science · doi:10.1126/science.281.5381.1309 · Cited by 9,051
MACDONALD, M. (1993) · Cell · doi:10.1016/0092-8674(93)90585-e · Cited by 8,366
(1978) · Biochemical Education · doi:10.1016/0307-4412(78)90049-3 · Cited by 5,073
Mitochondrial control of cell death
Kroemer, G., & Reed, J. C. (2000) · Nature Medicine · doi:10.1038/74994 · Cited by 3,103
The mitochondrial permeability transition pore and its role in cell death
CROMPTON, M. (1999) · Biochemical Journal · doi:10.1042/bj3410233 · Cited by 2,432
Neuropathological Classification of Huntingtonʼs Disease
VONSATTEL, J.-P., MYERS, R. H., STEVENS, T. J., FERRANTE, R. J., BIRD, E. D., & RICHARDSON, E. P. (1985) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-198511000-00003 · Cited by 2,227
Bax directly induces release of cytochrome c from isolated mitochondria
Jürgensmeier, J. M., Xie, Z., Deveraux, Q. L., Ellerby, L., Bredesen, D. E., & Reed, J. C. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.9.4997 · Cited by 1,523
Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila
Steffan, J. S., Bodai, L., Pallos, J., Poelman, M., McCampbell, A., Apostol, B. L., Kazantsev, A., Schmidt, E., Zhu, Y.-Z., Greenwald, M., et al. (2001) · Nature · doi:10.1038/35099568 · Cited by 1,228
Nucifora, F. C., Sasaki, M., Peters, M. F., Huang, H., Cooper, J. K., Yamada, M., Takahashi, H., Tsuji, S., Troncoso, J. C., Dawson, V. L., et al. (2001) · Science · doi:10.1126/science.1056784 · Cited by 1,112
Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines
Panov, A. V., Gutekunst, C.-A., Leavitt, B. R., Hayden, M. R., Burke, J. R., Strittmatter, W. J., & Greenamyre, J. T. (2002) · Nature Neuroscience · doi:10.1038/nn884 · Cited by 1,030
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The amyloid state of proteins: A boon or bane?
Hassan, M. N., Nabi, F., Khan, A. N., Hussain, M. S., Siddiqui, W. A., Uversky, V. N., & Khan, R. H. (2022) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2022.01.115 · Cited by 30
Mitochondrial dynamic changes in health and genetic diseases
Chen, L., Winger, A. J., & Knowlton, A. A. (2014) · Molecular Biology Reports · doi:10.1007/s11033-014-3663-y · Cited by 31
“Studies have demonstrated the localization of mutant Htt to the outer mitochondrial membrane using both HD transgenic mice and HD striatal cells (STHdhQ111) [66].”
Progressive hepatic mitochondrial dysfunction in premanifest Huntington's disease
Hoffmann, R., Stüwe, S. H., Goetze, O., Banasch, M., Klotz, P., Lukas, C., Tegenthoff, M., Beste, C., Orth, M., & Carsten Saft, C. (2014) · Movement Disorders · doi:10.1002/mds.25862 · Cited by 28
“A direct interaction of mutant Huntingtin with mitochondria was demonstrated in isolated mouse liver.(3) Methionine, an essential amino acid, is metabolized in mitochondria of the liver.”
BackgroundAltered Ca2+ signaling in skeletal muscle fibers of the R6/2 mouse, a model of Huntington’s disease
Braubach, P., Orynbayev, M., Andronache, Z., Hering, T., Landwehrmeyer, G. B., Lindenberg, K. S., & Melzer, W. (2014) · The Journal of General Physiology · doi:10.1085/jgp.201411255 · Cited by 28
“…studies, demonstrating the effects of mhtt on cellular energetics and Ca2+ regulation (Arenas et al., 1998; Lodi et al., 2000; Panov et al., 2002; Choo et al., 2004; Gellerich et al., 2004, 2008; Saft et al., 2005; Gizatullina et al., 2006; Lin and Beal, 2006; Turner et al., 2007; Bossy-Wetzel…”
BackgroundMaiuri, T., Bowie, L. E., & Truant, R. (2018) · DNA and Cell Biology · doi:10.1089/dna.2018.4476 · Cited by 28
“…and function in human HD lymphoblasts, post-mortem HD patient brain specimens, and HD mouse model neurons (Gu et al. , 1996; Panov et al. , 2002; Choo et al. , 2004; Squitieri et al. , 2006; Song et al. , 2011; Napoli et al. , 2013; Yano et al. , 2014), leading to hypotheses for direct…”
Agrawal, S., & Fox, J. H. (2019) · Mitochondrion · doi:10.1016/j.mito.2019.03.004 · Cited by 28
“Electron microscopic and fractionation studies provide evidence for association of mhtt with the outer mitochondrial membrane (Choo et al., 2004; Panov et al., 2002).”
BackgroundProteomic analysis of mitochondrial dysfunction in neurodegenerative diseases
Rodolfo, C., Ciccosanti, F., Giacomo, G. D., Piacentini, M., & Fimia, G. M. (2010) · Expert Review of Proteomics · doi:10.1586/epr.10.43 · Cited by 29
Peixoto, P. M. V., Dejean, L. M., & Kinnally, K. W. (2011) · Mitochondrion · doi:10.1016/j.mito.2011.03.003 · Cited by 29
“One study has shown that mutant huntingtin reduces the calcium load needed to induce PTP opening (Choo et al., 2004).”
BackgroundMolecular mechanism of PANoptosis and programmed cell death in neurological diseases
Hou, K., Pan, W., Liu, L.-Y., Yu, Q., Ou, J. T., Li, Y., Yang, X., Lin, Z., Yuan, J. H., & Fang, M. (2025) · Neurobiology of Disease · doi:10.1016/j.nbd.2025.106907 · Cited by 31
“Furthermore, mHTT upregulates pro-apoptotic factors such as BIM (Bcl-2 interacting mediator of cell death) and Bcl2-associated X protein (Bax), triggering mitochondrial dysfunction and cytochrome c release (Choo et al., 2004; Sawa et al., 1999; Y. Zhang et al., 2003).”
Cherubini, M., & Ginés, S. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.08.042 · Cited by 28
Szalárdy, L., Zádori, D., Klivènyi, P., Toldi, J., & Vécsei, L. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2015/498401 · Cited by 30
Deschepper, M., Hoogendoorn, B., Brooks, S. P., Dunnett, S. B., & Jones, L. (2011) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2011.01.012 · Cited by 27
Sphingolipids and impaired hypoxic stress responses in Huntington disease
Burtscher, J., Pepe, G., Maharjan, N., Riguet, N., Pardo, A. D., Maglione, V., & Millet, G. P. (2023) · Progress in Lipid Research · doi:10.1016/j.plipres.2023.101224 · Cited by 27
Veres, G., Molnar, M. F., Zádori, D., Szentirmai, M., Szalárdy, L., Maszlag-Török, R., Fazekas, E., Ilisz, I., Vécsei, L., & Klivènyi, P. (2015) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2015.03.002 · Cited by 28
“Furthermore, mHtt has been shown to be able to bind directly to the mitochondria, altering their normal function (Choo et al., 2004).”
Assessing Mitochondrial Function in In Vitro and Ex Vivo Models of Huntington’s Disease
Ferreira, I. L., Carmo, C., Naia, L., Mota, S. I., & Rego, A. C. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-7825-0_19 · Cited by 25
Truong, T. T., Singh, A. A., Bang, N. V., Vu, N. M. H., Na, S., Choi, J., Oh, J., & Mondal, S. (2025) · Membranes · doi:10.3390/membranes15090263 · Cited by 25
Metabotropic glutamate receptor 5 as a potential therapeutic target in Huntington’s disease
Ribeiro, F. M., Hamilton, A., Doria, J. G., Guimaraes, I. M., Cregan, S. P., & Ferguson, S. S. G. (2014) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2014.948419 · Cited by 26
“Moreover, polyglutamine-expanded htt destabilizes mitochondrial Ca regulation [47,48].”
BackgroundMitochondrial Respiratory Function in Peripheral Blood Cells from Huntington's Disease Patients
Ehinger, J. K., Morota, S., Hansson, M. J., Paul, G., & Elmér, E. (2016) · Movement Disorders Clinical Practice · doi:10.1002/mdc3.12308 · Cited by 25
Hamilton, J., Brustovetsky, T., & Brustovetsky, N. (2017) · Neurochemistry International · doi:10.1016/j.neuint.2017.01.001 · Cited by 24
“This is consistent with our previous data (Hamilton et al., 2015) andwith results from others (Choo et al., 2004).”
BackgroundResultInfluentialLiu, D., McIlvain, H. B., Fennell, M., Dunlop, J., Wood, A., Zaleska, M. M., Graziani, E. I., & Pong, K. (2007) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2007.03.018 · Cited by 24
Mitochondrial contributions to neuronal development and function
Princz, A., Kounakis, K., & Tavernarakis, N. (2018) · Biological Chemistry · doi:10.1515/hsz-2017-0333 · Cited by 25
“, 2008), due to direct interaction of mutant Htt with the organelles (Panov et al., 2002; Choo et al., 2004).”
BackgroundSantos‐Miranda, A., Cardozo, P. L., da Silva, F. R., de Souza, J. M., Olmo, I. G., Cruz, J. S., Gomez, M. V., Ribeiro, F. M., & Vieira, L. B. (2019) · ASN NEURO · doi:10.1177/1759091419856811 · Cited by 23
Iuliano, M., Seeley, C., Sapp, E., Jones, E. L., Martin, C., Li, X., DiFiglia, M., & Kegel-Gleason, K. B. (2021) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2021.618391 · Cited by 22
Mitochondrial membranes modify mutant huntingtin aggregation
Adegbuyiro, A., Sedighi, F., Jain, P., Pinti, M. V., Siriwardhana, C., Hollander, J. M., & Legleiter, J. A. (2021) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2021.183663 · Cited by 24
Gómez-Jaramillo, L., Cano-Cano, F., González-Montelongo, M. D. C., Campos‐Caro, A., Aguilar‐Diosdado, M., & Arroba, A. I. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23116089 · Cited by 23
“mHTT directly induced mitochondrial permeability transition (MPT) pore opening in isolated mouse liver mitochondria of a CHL2 HD model [83] (Table 3).”
BackgroundSelective striatal mtDNA depletion in end-stage Huntington's disease R6/2 mice
Hering, T., Birth, N., Taanman, J., & Orth, M. (2015) · Experimental Neurology · doi:10.1016/j.expneurol.2015.02.004 · Cited by 23
“…protein (HTT) is predominantly found in the cytoplasm where some HTT associates with the plasma membrane, mitochondria, lysosomes and the endoplasmatic reticulum (Atwal and Truant, 2008; Choo et al., 2004; Kegel et al., 2000, 2002; Orr et al., 2008; Panov et al., 2002; Strehlow et al., 2007).”
Effects of estrogens and androgens on mitochondria under normal and pathological conditions
Mohajeri, M., Martín-Jiménez, C., Barreto, G. E., & Sahebkar, A. (2019) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2019.03.001 · Cited by 23
“The enhanced susceptibility of the mitochondria to the Cainduced permeability transition and cytochrome c production (Choo et al., 2004) damages mitochondrial trafficking (Trushina et al.”
Filippo, M. D., Picconi, B., Costa, C., Bagetta, V., Tantucci, M., Parnetti, L., & Calabresi, P. (2006) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2006.06.024 · Cited by 25
Expression of polyalanine stretches induces mitochondrial dysfunction
Toriumi, K., Oma, Y., Kino, Y., Futai, E., Sasagawa, N., & Ishiura, S. (2008) · Journal of Neuroscience Research · doi:10.1002/jnr.21619 · Cited by 22
“Mitochondria isolated from cells expressing mutated huntingtin show decreased membrane potential, a defect in Ca(21) homeostasis, and higher susceptibility to a Ca(21)-induced permeability transition (Sawa et al., 1999; Panov et al., 2003; Choo et al., 2004).”
BackgroundInfluentialNew opportunities for antioxidants in amelioration of neurodegenerative diseases
Bhandari, U. R., Danish, S. M., Ahmad, S., Ikram, M., Nadaf, A., Hasan, N., Kesharwani, P., & Ahmad, F. J. (2024) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2024.111961 · Cited by 24
Bioenergetics in fibroblasts of patients with Huntington disease are associated with age at onset
Gardiner, S. L., Milanese, C., Boogaard, M. W., Buijsen, R. A. M., Hogenboom, M., Roos, R. A. C., Mastroberardino, P. G., van Roon‐Mom, W., & Aziz, N. A. (2018) · Neurology Genetics · doi:10.1212/nxg.0000000000000275 · Cited by 20
“Possible hypotheses include the direct association of mutant HTT with the mitochondrial membrane, causing decreased import of subunits into the mitochondria, increased degradation, or abnormal assembly.(13,29,30) Furthermore, mutant HTT has been shown to increase cellular oxidative stress, which was associated with im…”
BackgroundRNA-Targeting CRISPR/CasRx system relieves disease symptoms in Huntington’s disease models
Lin, Y., Li, C., Chen, Y., Gao, J., Li, J., Huang, C., Liu, Z., Wang, W., Zheng, X., Song, X., et al. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-024-00794-w · Cited by 26
Dagar, S., Sharma, M., Tsaprailis, G., Scharager-Tapia, C., Crynen, G. C., Joshi, P. S., Shahani, N., & Subramaniam, S. (2024) · Molecular & Cellular Proteomics · doi:10.1016/j.mcpro.2024.100746 · Cited by 20
Singer, E., Walter, C., Weber, J. J., Krahl, A.-C., Mau-Holzmann, U. A., Rischert, N., Rieß, O., Clemensson, L. E., & Nguyen, H. P. (2017) · Scientific Reports · doi:10.1038/s41598-017-17275-4 · Cited by 20
MERCs. The Novel Assistant to Neurotransmission?
Shirokova, O. M., Pchelin, P. V., & Mukhina, I. V. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.589319 · Cited by 20
“, 2002) and truncated N-terminal mHtt (Choo et al., 2004) exposure.”
BackgroundNMDA Receptors and Huntington’s Disease
Fernandes, H. B., & Raymond, L. A. (2008) · Frontiers in neuroscience · doi:10.1201/9781420044157.ch2 · Cited by 21
Islam, M. R., Jony, M. H., Thufa, G. K., Akash, S., Dhar, P. S., Rahman, M. M., Afroz, T., Ahmed, M., Hemeg, H. A., Rauf, A., et al. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03604-4 · Cited by 20
“Not to mention, some interactions, like a number of proteins [56] that possess WW domains, can bind to the HTT exon1 proline-rich domain (PRD) [57].”
Experimental Models of HD and Reflection on Therapeutic Strategies
Kim, J., Bordiuk, O. L., & Ferrante, R. J. (2011) · International review of neurobiology · doi:10.1016/b978-0-12-381328-2.00016-x · Cited by 20
Naia, L., Ribeiro, M. J., & Rego, A. C. (2011) · Reviews in the Neurosciences · doi:10.1515/rns.2011.060 · Cited by 19
Calcium Handling by Endoplasmic Reticulum and Mitochondria in a Cell Model of Huntington’s Disease
Mario, A. D., Scarlatti, C., Costiniti, V., Primerano, S., Lopreiato, R., Calí, T., Brini, M., Giacomello, M., & Carafoli, E. (2016) · PLoS Currents · doi:10.1371/currents.hd.37fcb1c9a27503dc845594ee4a7316c3 · Cited by 19
“Wild-type (18Q) and mutant (150Q) cDNA of human IT15 exon 1 gene, encoding the N-terminal (1-90) region of the Htt protein, have been obtained by PCR amplification using as template the plasmid pIND-HD exon 1- EGFP 150Q (Wang, 1999) and the following primers, inserting the EcoRV and BamHI at the 5’- and 3’-ends, respe…”
Polyglutamine Disorders Including Huntington's Disease
Todi, S. V., Williams, A. J., & Paulson, H. L. (2007) · Elsevier eBooks · doi:10.1016/b978-012369509-3.50019-6 · Cited by 19
Neurons and astrocytes have distinct organelle signatures and responses to stress
Rhoads, S. N., Dong, W., Hsu, C.-H., Mfulama, N. R., Yarlagadda, R., Ragusa, J. V., Ye, M. Y., Henrie, A., Zanellati, M. C., Diering, G. H., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116280 · Cited by 22
Mitochondrial biogenesis in organismal senescence and neurodegeneration
Daskalaki, I., & Tavernarakis, N. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111345 · Cited by 18
Beasley, M. A., Frazee, N. C., Groover, S. E., Valentine, S. J., Mertz, B., & Legleiter, J. A. (2022) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.1c10254 · Cited by 18
Mitochondria: how eminent in ageing and neurodegenerative disorders?
Bamshad, C., Najafi-Ghalehlou, N., Pourmohammadi-Bejarpasi, Z., Tomita, K., Kuwahara, Y., Sato, T., Feizkhah, A., Roushnadeh, A. M., & Roudkenar, M. H. (2022) · Human Cell · doi:10.1007/s13577-022-00833-y · Cited by 20
Mitochondrial calcium handling and neurodegeneration: when a good signal goes wrong
Filadi, R., & Pizzo, P. (2020) · Current Opinion in Physiology · doi:10.1016/j.cophys.2020.08.009 · Cited by 18
Onikanni, S. A., Lawal, B., Oyinloye, B. E., Ajiboye, B. O., Sukhbat, U., Wang, C., Emran, T. B., & Simal‐Gándara, J. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.121247 · Cited by 19
Emergence of breath testing as a new non-invasive diagnostic modality for neurodegenerative diseases
Subramaniam, N. S., Bawden, C. S., Waldvogel, H. J., Faull, R. L. M., Howarth, G. S., & Snell, R. G. (2018) · Brain Research · doi:10.1016/j.brainres.2018.04.017 · Cited by 17
Li, H., Uittenbogaard, M. N., Hao, L., & Chiaramello, A. (2021) · Metabolites · doi:10.3390/metabo11040233 · Cited by 18
“The mutated Htt protein can directly interact with the OMM, triggering the loss of mitochondrial membrane potential and permeability [90].”
BackgroundHSF1 and Its Role in Huntington’s Disease Pathology
Kim, H., & Gómez‐Pastor, R. (2022) · Advances in experimental medicine and biology · doi:10.1007/5584_2022_742 · Cited by 21
Cholesterol impacts the formation of huntingtin/lipid complexes and subsequent aggregation
Stonebraker, A. R., Beasley, M. A., Massinople, S. E., Wunder, M. M., Li, P., Valentine, S. J., & Legleiter, J. A. (2023) · Protein Science · doi:10.1002/pro.4642 · Cited by 16
“…of membranes of varying lipid composition, localizing to the ER (Atwal et al., 2007; De Rooij, 1996; Xia, 2003), mitochondrial (Chang et al., 2006; Choo, 2004; Gu et al., 1996; Orr et al., 2008; Panov et al., 2002), nuclear (Atwal et al., 2007; Xia, 2003), and plasma membranes (Kegel et al.,…”
BackgroundHuntington’s disease: novel therapeutic perspectives hanging in the balance
Saavedra, A., Barriga, G. G.-D., Pérez‐Navarro, E., & Alberch, J. (2018) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2018.1465930 · Cited by 18
“Expression of mHtt alters mitochondrial function in peripheral tissues from HD patients ([61–64] and references therein), and mouse models [65,66].”
BackgroundHuang, C., Wang, K.-C., Yang, Y.-C., Chiou, C., Tan, C.-H., Lin, Y., & Huang, N. (2017) · Phytomedicine · doi:10.1016/j.phymed.2017.12.017 · Cited by 16
Mutant huntingtin fails to directly impair brain mitochondria
Hamilton, J., Brustovetsky, T., & Brustovetsky, N. (2019) · Journal of Neurochemistry · doi:10.1111/jnc.14852 · Cited by 15
Lautenschläger, J., & Schierle, G. S. K. (2019) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2019.101660 · Cited by 16
Restoration of c-Src/Fyn Proteins Rescues Mitochondrial Dysfunction in Huntington's Disease
Fão, L., Coelho, P., Duarte, L., Vilaça, R., Hayden, M. R., Mota, S. I., & Rego, A. C. (2022) · Antioxidants and Redox Signaling · doi:10.1089/ars.2022.0001 · Cited by 14
“…(45) and different HD cellular ( e.g ., human neuroblastoma cells and platelets, mouse striatal ST Hdh Q111/Q111 cells) and animal models [Hdh(CAG)150 knock-in mouse] showed HTT fragments in close contact with mitochondria (3, 23, 38), supporting a direct effect of mHTT on mitochondrial function.”
Buck, E., Zügel, M., Schümann, U., Merz, T., Gumpp, A. M., Witting, A., Steinacker, J. M., Landwehrmeyer, G. B., Weydt, P., Calzia, E., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0175248 · Cited by 18
Tao, L., Liu, X., Da, W., Tao, Z., & Zhu, Y. (2020) · Neurological Research · doi:10.1080/01616412.2020.1773610 · Cited by 15
Marubuchi, S., Wada, Y., Okuda, T., Hara, Y., Qi, M., Hoshino, M., Nakagawa, M., Kanazawa, I., & Okazawa, H. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03405.x · Cited by 15
Macromolecular crowding in solution alters huntingtin interaction and aggregation at interfaces
Groover, S. E., Adegbuyiro, A., Fan, C. K., Hodges, B. L., Beasley, M. A., Taylor, K., Stonebraker, A. R., Siriwardhana, C., & Legleiter, J. A. (2021) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2021.111969 · Cited by 15
Singhal, K., & Sandhir, R. (2014) · Journal of Neuroscience Research · doi:10.1002/jnr.23478 · Cited by 15
“, 1987), alterations in mitochondrial and endoplasmic reticulum (ER) calcium homeostasis (Hirai et al., 2001; Choo et al., 2004), glutamate excitotoxicity (Mattson et al.”
BackgroundKumar, A., Kneynsberg, A., Tucholski, J., Perry, G. M., van Groen, T., Detloff, P. J., & Lesort, M. J. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2012.05.015 · Cited by 13
“, 2000), and mitochondrial dysfunction (Beal, 1994; Beal, 1996; Choo et al., 2004; Gu et al., 1996; Panov et al., 1999).”
BackgroundPhosphomimetic Mutations Impact Huntingtin Aggregation in the Presence of a Variety of Lipid Systems
Groover, S. E., Beasley, M. A., Ramamurthy, V., & Legleiter, J. A. (2020) · Biochemistry · doi:10.1021/acs.biochem.0c00788 · Cited by 15
Imaging mitochondrial calcium dynamics in the central nervous system
Serrat, R., Oliveira-Pinto, A., Marsicano, G., & Pouvreau, S. (2022) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2022.109560 · Cited by 13
Scholefield, M., Patassini, S., Xu, J., & Cooper, G. J. S. (2023) · EBioMedicine · doi:10.1016/j.ebiom.2023.104824 · Cited by 13
“35 Opening of the MPT can lead to further Ca in fl ux, mitochondrial swelling, and cell death.”
BackgroundPoration of mitochondrial membranes by amyloidogenic peptides and other biological toxins
Vassallo, N. (2024) · Journal of Neurochemistry · doi:10.1111/jnc.16213 · Cited by 13
“Mutant Htt also induced mPT pore opening accompanied by a significant release of cyto c (Choo et al., 2004 ).”
Mitochondrial Biology and the Identification of Biomarkers of Huntington’s Disease
Neueder, A., & Orth, M. (2020) · Neurodegenerative Disease Management · doi:10.2217/nmt-2019-0033 · Cited by 13
Mutant huntingtin does not cross the mitochondrial outer membrane
Hamilton, J., Brustovetsky, T., Khanna, R., & Brustovetsky, N. (2020) · Human Molecular Genetics · doi:10.1093/hmg/ddaa185 · Cited by 13
“treated mitochondria isolated from SH-SY5Y cells with trypsin and found that wild-type huntingtin (wtHTT) was completely degraded whereas voltage-dependent anion channel (VDAC), cytochrome c oxidase and cytochrome c (Cyt c) were spared (3).”
BackgroundMethodInfluentialMarquette, A., Aisenbrey, C., & Bechinger, B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22136725 · Cited by 13
“Finally, a mitochondrial malfunction has also been associated with the pathogenesis of Huntington’s disease [22,23].”
BackgroundOxidation Promotes Distinct Huntingtin Aggregates in the Presence and Absence of Membranes
Adegbuyiro, A., Stonebraker, A. R., Sedighi, F., Fan, C. K., Hodges, B. L., Li, P., Valentine, S. J., & Legleiter, J. A. (2022) · Biochemistry · doi:10.1021/acs.biochem.2c00212 · Cited by 15
Ali, M., Rao, K. B. N., Majumder, P., Sarkar, R., & Mapa, K. (2020) · Mitochondrion · doi:10.1016/j.mito.2020.12.003 · Cited by 13
Nekrasov, E. D., & Киселев, С. Л. (2018) · Journal of Stem Cells and Regenerative Medicine · doi:10.46582/jsrm.1402012 · Cited by 13
“There were some controversial reports on mitochondria isolated from patients or transgenic models investigating the effects of calcium concentration on mitochondria function([36-38]).”
BackgroundUnknown roles of tau pathology in neurological disorders. Challenges and new perspectives
Olesen, M. A., Villavicencio-Tejo, F., Cuevas-Espinoza, V., & Quintanilla, R. A. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102594 · Cited by 12
Preclinical Nanomedicines for Polyglutamine-Based Neurodegenerative Diseases
Lee, L. K. C., Leong, L. I., Liu, Y., Luo, M., Chan, H. Y. E., & Choi, C. H. J. (2020) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.0c00506 · Cited by 12
Involvement of CRMP2 in Regulation of Mitochondrial Morphology and Motility in Huntington’s Disease
Brustovetsky, T., Khanna, R., & Brustovetsky, N. (2021) · Cells · doi:10.3390/cells10113172 · Cited by 12
Reed, A. L., Mitchell, W., Alexandrescu, A. T., & Alder, N. N. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1263420 · Cited by 13
The Mitochondrial Permeability Transition Pore
Morganti, C., Bonora, M., Sbano, L., Morciano, G., Aquila, G., Campo, G. C., Wieckowski, M. R., Giorgi, C., & Pinton, P. (2018) · Springer eBooks · doi:10.1007/978-3-319-73344-9_5 · Cited by 13
Oikonomou, K. D., Donzis, E. J., Bui, M. T. N., Cepeda, C., & Levine, M. S. (2021) · Journal of Neurophysiology · doi:10.1152/jn.00181.2021 · Cited by 11
Kapadia, K., Trojniak, A. E., Rodríguez, K. B. G., Klus, N. J., Huntley, C., McDonald, P. R., Roy, A., Frankowski, K. J., Aubé, J., & Muma, N. A. (2022) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.2c00305 · Cited by 10
Targeting N-type calcium channels in young-onset of some neurological diseases
Antunes, F. T. T., de Souza, A. H., Figueira, J., Binda, N. S., Carvalho, V. P. R., Vieira, L. B., & Gomez, M. V. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.1090765 · Cited by 10
Kynurenine 3-Monooxygenase Interacts with Huntingtin at the Outer Mitochondrial Membrane
Swaih, A. M., Breda, C., Sathyasaikumar, K. V., Allcock, N., Collier, M. E. W., Mason, R. P., Feasby, A., Herrera, F., Outeiro, T. F., Schwarcz, R. M., et al. (2022) · Biomedicines · doi:10.3390/biomedicines10092294 · Cited by 9
“While HTT is predominantly cytoplasmic and membrane-associated [21,22], mitochondrial localisation has been observed [23,24].”
BackgroundThe Role of Impaired Mitochondrial Transport in the Development of Neurodegenerative Diseases
Blagov, A. V., Borisov, E. E., Grechko, A. V., Popov, M. A., Sukhorukov, V. N., & Orekhov, A. N. (2023) · Journal of Integrative Neuroscience · doi:10.31083/j.jin2204086 · Cited by 9
“In cell models, it was found that huntingtin could cause disturbances in the maintenance of the mitochondrial membrane potential and mitochondrialmediated calcium traffic [49,50].”
BackgroundModulation of mitochondrial function by stem cell-derived cellular components
Liu, T., Im, W., Lee, S., Ban, J.-J., Chai, Y. J., Lee, M., Mook‐Jung, I., Chu, K., & Kim, M. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.04.129 · Cited by 9
Reviewing Biochemical Implications of Normal and Mutated Huntingtin in Huntington’s Disease
Tellone, E., Galtieri, A., & Ficarra, S. (2019) · Current Medicinal Chemistry · doi:10.2174/0929867326666190621101909 · Cited by 9
Insight into the Interactome of Intramitochondrial PKA Using Biotinylation-Proximity Labeling
Amer, Y. O., & Hébert-Chatelain, É. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21218283 · Cited by 9
“The trypsin sensitivity assay was carried out as described previously [47] with minor modifications.”
MethodPhysiopathologie de la maladie de Huntington : état des connaissances
Roze, E. F., Bétuing, S., Deyts, C., Vidailhet, M., & Caboche, J. (2008) · Revue Neurologique · doi:10.1016/j.neurol.2008.03.006 · Cited by 11
The Molecular Architecture of Neurodegeneration: An Integrative Overview of Convergent Mechanisms
Aranda-Abreu, G. E., Rojas-Durán, F., Hernández‐Aguilar, M. E., Herrera‐Covarrubias, D., Tlapa-Monge, L. R., & Mestizo-Gutiérrez, S. L. (2026) · NeuroSci · doi:10.3390/neurosci7010007 · Cited by 11
“In HD, the mutant huntingtin protein interferes with the function of mitochondrial permeability transition pore proteins, triggering apoptosis [20,21].”
Promethazine protects against 3-nitropropionic acid-induced neurotoxicity
Cléren, C., Calingasan, N. Y., Starkov, A. A., Jacquard, C., Chen, J., Brouillet, E., & Beal, M. F. (2009) · Neurochemistry International · doi:10.1016/j.neuint.2009.10.006 · Cited by 8
“Mitochondrial dysfunction and impaired calcium regulation have been shown in both HD transgenic mice as well as in lymphoblasts from patients (Panov et al., 2002; Choo et al., 2004).”
BackgroundAngiotensins and Huntington’s Disease: A Study on Immortalized Progenitor Striatal Cell Lines
Mello, W. C. D., Gerena, Y., & Ayala‐Peña, S. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00108 · Cited by 8
Rozas, E. E., & de Freitas, J. C. (2008) · Revista Brasileira de Farmacognosia · doi:10.1590/s0102-695x2008000100012 · Cited by 8
“…AD show mitochondria dysfunction in relation to the respective proteins, huntingtin and -amyloid, that increases the mitochondrial permeability transition, the cytochrome c release, reduces cytochrome oxidase activity, elevates ROS and reduces ATP level (Choo et al., 2004; Cardoso et al., 2004).”
BackgroundExpanded and Wild-type Ataxin-3 Modify the Redox Status of SH-SY5Y Cells Overexpressing α-Synuclein
Noronha, C., Perfeito, R., Laço, M., Wüllner, U., & Rego, A. C. (2017) · Neurochemical Research · doi:10.1007/s11064-017-2199-7 · Cited by 8
“Altered mitochondrial structure and deregulated mitochondrial activity, including increased caspase pathway activation and mitochondrial swelling, were previously linked to polyQ disorders [41].”
BackgroundMoldovean‐Cioroianu, N. S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25126789 · Cited by 8
Mitochondrial-Derived Peptides: Implication in the Therapy of Neurodegenerative Diseases
Thakur, R., Chauhan, A., Moudgil, H., Singh, S., & Devi, R. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05198-5 · Cited by 7
“…interacts with transcription regulators, such as p53, cAMP response element-binding (CREB) protein, and CREB-binding protein (CBP), involved in cell proliferation and survival; PGC-1α (peroxisome proliferator-activating receptor-γ coactivator-1 α), which is necessary for energy metabolism [66].”
Tu, Y., Li, X., Zhu, X., Liu, X., Guo, C., Jia, D., & Tang, T.-S. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.619911 · Cited by 8
Charge within Nt17 peptides modulates huntingtin aggregation and initial lipid binding events
Stonebraker, A. R., Hankin, R., Kapp, K. L., Li, P., Valentine, S. J., & Legleiter, J. A. (2023) · Biophysical Chemistry · doi:10.1016/j.bpc.2023.107123 · Cited by 8
Gil‐Mohapel, J., & Rego, A. C. (2001) · Revista Neurociências · doi:10.34024/rnc.2011.v19.8332 · Cited by 7
Kraskovskaya, N., & Борисович, Б. И. (2021) · Biochemistry (Moscow) · doi:10.1134/s0006297921040076 · Cited by 7
Cunha‐Oliveira, T., Lusa, I., & Cristina, A. (2012) · InTech eBooks · doi:10.5772/32728 · Cited by 6
“Indeed, mHtt interaction with neuronal mitochondria of YAC72 transgenic mice (Panov et al. 2002) was directly linked to mitochondrial calcium abnormalities (Choo et al. 2004;Panov et al. 2002).”
Background5.3 Mitochondrial Production of Oxidants and Their Role in the Regulation of Cellular Processes
Brookes, P. S. (2007) · Springer eBooks · doi:10.1007/978-0-387-30411-3_19 · Cited by 7
Multi-epitope immunocapture of huntingtin reveals striatum-selective molecular signatures
(2025) · doi:10.1038/s44320-025-00096-3 · Cited by 7
“Calcium dyshomeostasis is a unifying feature of HD models (Giacomello et al, 2013) and mutant HTT contributes to calcium-linked cell death via membrane permeability of the mitochondria (Choo et al, 2004), supporting that our striatum-enriched HIPs correlate to processes linked to HD pathobiology.”
Metadata
- Authors
- Choo, Y. S.
- Affiliations
- University of Alabama at Birmingham (US)
- Corresponding author
- Choo, Y. S.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-05-05
- Volume
- 13
- Issue
- 14
- Pages
- 1407-1420
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2100103422
- Cited by
- 515
- References
- 56
- Citations by year
- 2026: 12 · 2025: 16 · 2024: 14 · 2023: 22 · 2022: 28 · 2021: 34 · 2020: 27 · 2019: 21 · 2018: 24 · 2017: 19 · 2016: 21 · 2015: 23 · 2014: 27 · 2013: 17 · 2012: 35
- FWCI
- 9.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Hereditary Disease Foundation
- National Institute of Neurological Disorders and Stroke (R01NS041552, R01NS041744, NS32765, NS41744, R01NS032765, NS41552)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- mutant huntingtin, Huntington's disease, mitochondrial permeability transition, cytochrome c release, cyclosporine, mitochondrial outer membrane, polyglutamine expansion, striatal neurons
- MeSH terms
- Huntingtin Protein, Mitochondrial Permeability Transition Pore, Adenosine Triphosphate, Animals, Calcium, Cell Line, Humans, Huntington Disease, Intracellular Membranes, Ion Channels, Mitochondria, Liver, Mutation, Nerve Tissue Proteins, Nuclear Proteins, Recombinant Proteins, Cyclosporine, Mitochondrial Membrane Transport Proteins, Cytochromes c, Serotonin Plasma Membrane Transport Proteins, Mice
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