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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Ubiquitin pathways in neurodegenerative disease
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“Indeed, there is evidence from an HD mouse model (YAC72) and from cultured HD striatal neurons expressing endogenous mutant huntingtin (STHdhQ111) that this mutant protein associates directly with the outer mitochondrial membrane (Choo et al., 2004).”
BackgroundDevelopment or disease: duality of the mitochondrial permeability transition pore
Maria Jose Perez, J., & Quintanilla, R. A. (2017) · Developmental Biology · doi:10.1016/j.ydbio.2017.04.018 · Cited by 131
“Similarly, in HD, it was shown that mutant huntingtin affects mitochondrial function by modifying mitochondrial calcium homeostasis, mitochondrial morphology, and ROS handling through the opening of mPTP (Brustovetsky et al., 2003; Choo et al., 2004; Milakovic et al., 2006; Quintanilla et al., 2013, 2016).”
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Consensus Paper: Pathological Mechanisms Underlying Neurodegeneration in Spinocerebellar Ataxias
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Mitochondrial Ca2+ and neurodegeneration
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Mitochondrial dynamics, a key executioner in neurodegenerative diseases
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“Furthermore, increasing evidence suggests that mitochondrial dysfunction may be central to the pathogenesis of HD (6, 12, 15, 48).”
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Abramov, A. Y., Potapova, E., Владимирович, Д. В., & Dunaev, A. (2020) · Life · doi:10.3390/life10070101 · Cited by 129
Iron dysregulation in Huntington's disease
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“…dysfunction plays an important role in HD pathogenesis (Albin and Greenamyre,1992; Beal, 1992; Jenkins et al., 1993; Sawa et al., 1999; Panov et al., 2002; Choo et al., 2004; Tang et al., 2005; Oliveira et al., 2006, 2007; Shehadeh et al., 2006; Fernandes et al., 2007; Trushina and McMurray, 2007).”
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“Indeed, fulllength mHtt was found associated with the mitochondrial outer membrane in HdhQ111 cells (Choo et al., 2004), whereas N-terminal mHtt in R6/2micewas found associatedwith the surface of themitochondrial membrane, but also clustered within degenerating mitochondria (Yu et al., 2003).”
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Modesti, L., Danese, A., Vitto, V. A. M., Ramaccini, D., Aguiari, G., Gafà, R., Lanza, G., Giorgi, C., & Pinton, P. (2021) · Cells · doi:10.3390/cells10061317 · Cited by 123
A Mitochondria-Associated Oxidative Stress Perspective on Huntington’s Disease
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The Interplay between Ca2+ Signaling Pathways and Neurodegeneration
Ureshino, R. P., Erustes, A. G., Bassani, T. B., Wachilewski, P., Guarache, G. C., Nascimento, A. C., Costa, A. J., Smaili, S. S., & Pereira, G. J. S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20236004 · Cited by 122
“Additionally, it has been reported that mHtt strongly associates with mitochondrial proteins [131], and studies using HD animal models suggest that mHtt directly stimulates mPTP opening and cytochrome c release, even at lower Ca2+ concentrations, and triggers neuronal apoptosis [132].”
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“, 2005), and mHtt appears to directly facilitate the mPT by binding to mitochondrial membranes (Choo et al., 2004).”
BackgroundMitochondrial permeability transition pore induces mitochondria injury in Huntington disease
Quintanilla, R. A., Jin, Y. N., von Bernhardi, R., & Johnson, G. V. (2013) · Molecular Neurodegeneration · doi:10.1186/1750-1326-8-45 · Cited by 108
“Also, previous studies of mitochondria subfractionation indicated that huntingtin was associated with the outer mitochondrial membrane in striatal cells [20].”
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Markovinović, A., Greig, J., Martín‐Guerrero, S. M., Salam, S., & Paillusson, S. (2022) · Journal of Cell Science · doi:10.1242/jcs.248534 · Cited by 123
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Calcium-Handling Defects and Neurodegenerative DiseasePreprint
Schrank, S., Barrington, N. M., & Stutzmann, G. E. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a035212 · Cited by 115
Oxidative Stress, Mitochondrial Dysfunction and the Mitochondria Theory of Aging
Kong, Y., Trabucco, S. E., & Zhang, H. (2014) · Interdisciplinary topics in gerontology and geriatrics · doi:10.1159/000358901 · Cited by 117
The Emerging Roles of Ferroptosis in Huntington’s Disease
Mi, Y., Gao, X., Xu, H., Cui, Y., Zhang, Y., & Gou, X. (2019) · NeuroMolecular Medicine · doi:10.1007/s12017-018-8518-6 · Cited by 115
Popoli, P., Blum, D. L., Martire, A., Ledent, C. A., Ceruti, S., & Abbracchio, M. P. (2007) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2006.12.005 · Cited by 111
“, 2004), promotes functional alterations of the organelle in response to calcium or apoptotic inducers (Sawa et al., 1999; Panov et al., 2002; Choo et al., 2004) and alters mitochondria trafficking (Chang et al.”
BackgroundOmega-3 fatty acids in neurodegenerative diseases: Focus on mitochondria
Eckert, G. P., Lipka, U., & Muller, W. E. (2012) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2012.05.006 · Cited by 111
“Mhtt thereby acts either directly [182,183,186,187] or indirectly through transcriptional dysregulation of genes involved in mitochondrial function.”
BackgroundMembrane Interactions of the Amphipathic Amino Terminus of Huntingtin
Michalek, M., Salnikov, E. S., Werten, S., & Bechinger, B. (2013) · Biochemistry · doi:10.1021/bi301325q · Cited by 105
Reddy, P. H. (2014) · Drug Discovery Today · doi:10.1016/j.drudis.2014.03.020 · Cited by 109
Mitochondrial Ca2+ in neurodegenerative disorders
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Huntington Disease and the Huntingtin Protein
Zheng, Z., & Diamond, M. I. (2012) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-385883-2.00010-2 · Cited by 118
Multifaceted deaths orchestrated by mitochondria in neurones
Nagley, P., Higgins, G. C., Atkin, J. D., & Beart, P. M. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.09.004 · Cited by 107
“Striatal cells expressing mutant Htt display increased Ca sensitivity of ∆Ψm and are more vulnerable to the complex II inhibitor, 3-nitropropionic acid [307, 308].”
BackgroundHands, S. L., Sajjad, M. U., Newton, M. J., & Wyttenbach, A. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.307587 · Cited by 106
Intihar, T. A., Martinez, E. A., & Gómez‐Pastor, R. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00103 · Cited by 103
Current progress of mitochondrial transplantation that promotes neuronal regeneration
Chang, C.-Y., Liang, M.-Z., & Chen, L. (2019) · Translational Neurodegeneration · doi:10.1186/s40035-019-0158-8 · Cited by 102
Mutant huntingtin disrupts mitochondrial proteostasis by interacting with TIM23
Yablonska, S., Ganesan, V., Ferrando, L. M., Kim, J., Pyzel, A. M., Baranova, O. V., Khattar, N. K., Larkin, T. M., Baranov, S. V., Chen, N., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1904101116 · Cited by 104
Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases
Xiang, Y., Song, X., & Long, D. (2024) · Archives of Toxicology · doi:10.1007/s00204-023-03660-8 · Cited by 116
Increased TRPC5 glutathionylation contributes to striatal neuron loss in Huntington’s disease
Hong, C., Seo, H., Kwak, M., Jeon, J., Jang, J., Jeong, E. M., Myeong, J., Hwang, Y. J., Ha, K., Kang, M. J., et al. (2015) · Brain · doi:10.1093/brain/awv188 · Cited by 101
“…significantly decreasing the calcium threshold necessary to trigger mitochondrial permeability transition (MPT) pore opening (Pias and Aw, 2002; Choo et al., 2004; Lin and Downloaded from https://academic.oup.com/brain/article-abstract/138/10/3030/2468700 by guest on 26 July 2018 Beal, 2006).”
BackgroundThe role of oxidative stress in Huntington’s disease: Are antioxidants good therapeutic candidates?
Gil-Mohapel, J., Brocardo, P., & Christie, B. (2014) · Current Drug Targets · doi:10.2174/1389450115666140115113734 · Cited by 101
Brustovetsky, N., LaFrance, R., Purl, K. J., Brustovetsky, T., Keene, C. D., Low, W. C., & Dubinsky, J. M. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03036.x · Cited by 101
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MicroRNAs Dysregulation and Mitochondrial Dysfunction in Neurodegenerative Diseases
Catanesi, M., d’Angelo, M., Tupone, M. G., Benedetti, E., Giordano, A., Castelli, V., & Cimini, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21175986 · Cited by 101
Jadiya, P., Garbincius, J. F., & Elrod, J. W. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01224-4 · Cited by 94
Polyglutamine expansion in huntingtin alters its interaction with phospholipids
Kegel, K. B., Sapp, E., Alexander, J. S., Valencia, A., Reeves, P., Li, X., Masso, N., Sobin, L. B., D, N. A. M., & DiFiglia, M. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06255.x · Cited by 94
Role of cerebral cortex in the neuropathology of Huntington's disease
Estrada‐Sánchez, A. M., & Rebec, G. V. (2013) · Frontiers in Neural Circuits · doi:10.3389/fncir.2013.00019 · Cited by 96
“In support of this mechanism, in vitro and in vivo studies indicate that mutant HTT disrupts gene expression, calcium buffering, and mitochondrial function (Choo et al., 2004; Milakovic and Johnson, 2005; Tang et al., 2005; Thomas et al., 2011).”
BackgroundThe role of deubiquitinating enzymes in apoptosis
Ramakrishna, S., Suresh, B., & Baek, K. (2010) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-010-0504-6 · Cited by 98
“the mitochondria [129, 130].”
Chou, A.-H., Yeh, T., Kuo, Y.-L., Kao, Y.-C., Jou, M., Hsu, C.-Y., Tsai, S.-R., Kakizuka, A., & Wang, H. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.07.011 · Cited by 94
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“Altered mitochondrial Ca(2) handling in HD cells has been previously implicated in HTT toxicity (69).”
BackgroundCalabrese, G., Molzahn, C. M., & Mayor, T. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102062 · Cited by 92
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“The presence of mutant Htt interferes with functions at mitochondrial membranes (Choo et al., 2004; Milakovic et al., 2006; Gellerich et al., 2008; Lim et al., 2008) and with epidermal growth factor (EGF) receptordependent signaling (Song et al.”
BackgroundLiang, H., Ran, Q., Jang, Y. C., Holstein, D. M., Lechleiter, J. D., McDonald-Marsh, T., Musatov, A., Song, W. J., Remmen, H. V., & Richardson, A. G. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.05.012 · Cited by 88
“It should be noted that in several studies, Cyt c has been found in the intermembrane space [41,42]; in these studies mitochondria were obtained from neuronal and kidney cell lines, whereas in our study liver mitochondria were isolated from mice.”
ResultGellerich, F. N., Gizatullina, Z. Z., Nguyen, H. P., Trumbeckaitė, S., Vielhaber, S., Seppet, E. K., Zierz, S., Landwehrmeyer, G. B., Rieß, O., von Hörsten, S., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m709555200 · Cited by 88
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Mitochondrial Inhibition and Oxidative Stress: Reciprocating Players in Neurodegeneration
Zeevalk, G. D., Bernard, L. P., Song, C., Gluck, M. J., & Ehrhart, J. (2005) · Antioxidants and Redox Signaling · doi:10.1089/ars.2005.7.1117 · Cited by 89
“This function for glutathione serves a primary role in protecting neurons from mitochondrial impairment .”
Mitochondrial quality control and neurological disease: an emerging connection
de Castro, I. P., Martins, L. M., & Tufi, R. (2010) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399410001456 · Cited by 92
“89).”
Wu, J., Jeong, H. K., Bulin, S. E., Kwon, S. W., Park, J. H., & Борисович, Б. И. (2009) · Journal of Neuroscience Research · doi:10.1002/jnr.22017 · Cited by 85
“, 2008), and destabilizing mitochondrial Ca(21) handling (Panov et al., 2002; Choo et al., 2004).”
BackgroundMitochondria and Energetic Depression in Cell Pathophysiology
Seppet, E. K., Puurand, M., Peetsalu, A., Gizatullina, Z. Z., Nguyen, H. P., Vielhaber, S., Wussling, M. H. P., Trumbeckaitė, S., Arandarčikaitė, O., Jerzembek, D., et al. (2009) · International Journal of Molecular Sciences · doi:10.3390/ijms10052252 · Cited by 84
“Indeed, decreased Ca accumulation capacities of mitochondria isolated from brain of YAC72Q mice [133], liver of htt111Q mice [134], HD patient’s lymphocytes [133], and htt111Q striatal progenitor cells [135] have been reported.”
BackgroundMitochondrial lipids in neurodegeneration
Aufschnaiter, A., Kohler, V., Diessl, J., Peselj, C., Carmona‐Gutiérrez, D., Keller, W., & Büttner, S. (2016) · Cell and Tissue Research · doi:10.1007/s00441-016-2463-1 · Cited by 91
“The wild-type as well as the mutant forms of Htt localize to the OMM, but only mutated variants directly induce mitochondrial membrane permeabilization (Choo et al. 2004).”
BackgroundTreating neurodegeneration by modifying mitochondria: potential solutions to a “complex” problem
Swerdlow, R. H. (2007) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1676 · Cited by 81
“One hypothesis suggests mutant huntingtin directly interacts with mitochondria, thereby interfering with calcium homeostasis (32, 121).”
Significance of Programmed Cell Death Pathways in Neurodegenerative Diseases
Guo, D., Liu, Z., Zhou, J., Ke, C., & Li, D. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25189947 · Cited by 83
“Meanwhile, mHTT proteins can cause mitochondrial dysfunction and the subsequent release of cytochrome c [270,271].”
BackgroundGanie, S. A., Dar, T. A., Bhat, A. H., Dar, K. B., Anees, S., Zargar, M. A., & Masood, A. (2015) · Rejuvenation Research · doi:10.1089/rej.2015.1704 · Cited by 80
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Jin, Y. N., & Johnson, G. V. W. (2010) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-010-9286-7 · Cited by 80
“Mitochondria isolated from a knock-in (150/150) HD mouse showed a similar increased susceptibility to Cainduced mPTP opening (Choo et al. 2004).”
BackgroundInfluentialTao, G., Looi, K., Toivola, D. M., Strnad, P., Zhou, Q., Liao, J., Wei, Y., Habtezion, A., & Omary, M. B. (2009) · Journal of Cell Science · doi:10.1242/jcs.051862 · Cited by 81
Mańczak, M., & Reddy, P. H. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv429 · Cited by 77
A mitochondrial ubiquitin ligase MITOL controls cell toxicity of polyglutamine-expanded protein
Sugiura, A., Yonashiro, R., Fukuda, T., Matsushita, N., Nagashima, S., Inatome, R., & Yanagi, S. (2010) · Mitochondrion · doi:10.1016/j.mito.2010.09.001 · Cited by 76
Signaling pathways regulating neuron–glia interaction and their implications in Alzheimer's disease
Lian, H., & Zheng, H. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13424 · Cited by 77
Impaired Redox Signaling in Huntington’s Disease: Therapeutic Implications
Paul, B. D., & Snyder, S. H. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00068 · Cited by 76
“mHtt interacts with the outer mitochondrial membrane and affects the mitochondrial permeability transition pore (mPTP), decreasing the Ca2+ threshold to trigger mPTP opening, and lowering ATP levels within the organelle (Choo et al., 2004).”
BackgroundMao, Z., Choo, Y. S., & Lesort, M. J. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.04686.x · Cited by 75
“…et al., 2004; Trushina et al., 2004), abnormal transcriptional regulation (Cha, 2000), synaptic dysfunction (Li et al., 2003), excitotoxic and oxidative damage (Beal, 1996; Browne et al., 1997, 1999) and mitochondria dysfunction (Browne et al., 1997; Panov et al., 2002; Choo et al., 2004).”
BackgroundMethodSelf-citationMembrane Interactions and Toxicity by Misfolded Protein Oligomers
Gonzalez-Garcia, M., Fusco, G., & Simone, A. D. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.642623 · Cited by 73
“In the context of Huntington’s disease (HD), mutant huntingtin (Htt) has been associated with the opening of mPTP in the inner mitochondrial membrane, triggering the release of cytochrome c and activating apoptosis (Choo et al., 2004).”
BackgroundSawant, N. A., Morton, H., Kshirsagar, S., Reddy, A. P., & Reddy, P. H. (2021) · Molecular Neurobiology · doi:10.1007/s12035-021-02556-x · Cited by 74
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“]. Huntingtin is detected throughout the cell, in the nucleus and in the cytoplasm, where it can associate with mitochondria [”
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“Indeed, it has been reported that (i) binding of mutHtt to OM increases mitochondria susceptibility to calcium-induced permeability transition pore opening and cytochrome c release (25) and (ii) the interaction of mutHtt with the OM protein Drp1 increases mitochondrial fragmentation and impairs mitochondrial biogenesi…”
BackgroundMitostasis, Calcium and Free Radicals in Health, Aging and Neurodegeneration
Godoy, J. A., Ríos, J. A., Picón-Pagès, P., Herrera-Fernández, V., Swaby, B., Crepin, G., Vicente, R., Fernández‐Fernández, J. M., & Muñoz, F. J. (2021) · Biomolecules · doi:10.3390/biom11071012 · Cited by 73
“Peroxynitrite is a highly reactive anion that nitrates proteins and lipids, which negatively impacts their physiological functions, especially in neurodegenerative diseases [156,168,169].”
BackgroundOlesen, M. A., Villavicencio-Tejo, F., & Quintanilla, R. A. (2022) · Translational Neurodegeneration · doi:10.1186/s40035-022-00308-y · Cited by 80
“Skin fibroblasts: a model to study pathological changes in AD, PD, HD, and ALS In recent years, there has been an urgent need to develop novel methodologies to understand how different inherited and sporadic NDs can compromise mitochondrial function and neuronal survival [116, 170, 203].”
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“Additionally, Htt protein is present in mitochondria of rat (Gutekunst et al., 1998), mouse, and human somatic cells(Choo et al., 2004) and therefore, may be important for mitochondrial activities.”
BackgroundImpaired mitochondrial trafficking in Huntington's disease
Li, X., Orr, A. L., & Li, S. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.06.008 · Cited by 70
“In vitro studies indicate that ΔΨm and mitochondrial Ca2+ regulation are directly impaired by mutant htt and that increased ROS generation is the driving force for these alterations [21-23].”
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“Studies in an HD mouse model and cultured HD striatal cells (STHdhQ111) show that mutant Htt associates directly with the outer mitochondrial membrane (6).”
BackgroundEnergy defects in Huntington's disease: Why “in vivo” evidence matters
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“This could be due to the interaction of mutant huntingtin with the OMM, which causes mitochondrial membrane potential reduction and potentiates mitochondrial permeability transition [250].”
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“It also prevents the binding of mPTP inhibitors, such as adenine nucleotides [135].”
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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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