The DOI matches its Crossref record; 21 of the 21 references it cites were found in a registry or an index.
Mitochondria‐targeted antioxidants protect Friedreich Ataxia fibroblasts from endogenous oxidative stress more effectively than untargeted antioxidants
Abstract
Friedreich Ataxia (FRDA), the most common inherited ataxia, arises from defective expression of the mitochondrial protein frataxin, which leads to increased mitochondrial oxidative damage. Therefore, antioxidants targeted to mitochondria should be particularly effective at slowing disease progression. To test this hypothesis, we compared the efficacy of mitochondria‐targeted and untargeted antioxidants derived from coenzyme Q 10 and from vitamin E at preventing cell death due to endogenous oxidative stress in cultured fibroblasts from FRDA patients in which glutathione synthesis was blocked. The mitochondria‐targeted antioxidant MitoQ was several hundredfold more potent than the untargeted analog idebenone. The mitochondria‐targeted antioxidant MitoVit E was 350‐fold more potent than the water soluble analog Trolox. This is the first demonstration that mitochondria‐targeted antioxidants prevent cell death that arises in response to endogenous oxidative damage. Targeted antioxidants may have therapeutic potential in FRDA and in other disorders involving mitochondrial oxidative damage.
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In the citing paper
“In other studies, the EC50 for MitoQ in cultured cells was <0.5 nM, and the protective effect then plateaued over several logs of concentration (Jauslin et al., 2003).”
From The mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer’s disease (2011) · cites this paper as Jauslin et al., 2003
In the citing paper
“There is extensive in vitro evidence that the concentrations of MitoQ used here have no impact on mitochondrial functions, such as ATP production, membrane potential, or ROS production in cells or mitochondria, but do prevent mitochondrial oxidative damage under conditions that lead to oxidative stress (Kelso et al., 2001; Jauslin et al., 2003; Saretzki et al., 2003; Asin-Cayuelaa et al., 2004).”
From The mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer’s disease (2011) · cites this paper as Jauslin et al., 2003
In the citing paper
“Mitochondrially-targeted coenzyme Q (MitoQ) or mitochondrially-targeted vitamin E (MitoVitE) have been shown to target mitochondrial dysfunction282,283.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [283]
In the citing paper
“Mitochondrial-targeted antioxidants protected Friedreich ataxia fibroblasts, in which glutathione synthesis was blocked, from oxidative stress (148)”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [148]
In the citing paper
“In glioma cells, astrocytes, and macrophages, Fpn associates with ceruloplasmin (Cp) (123, 148).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [148]
In the citing paper
“Inability to export iron may explain tissue iron accumulation.”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [148]
In the citing paper
“Adult Cp-knockout mice exhibited accumulation of iron in the cerebellum and brainstem that correlated with the development of deficits in coordination of movement (148).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [148]
In the citing paper
“GPI-anchored Cp was required for export of iron from astrocytes (148) (Table 4).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [148]
Citations
Cites
Friedreich's Ataxia: Autosomal Recessive Disease Caused by an Intronic GAA Triplet Repeat Expansion
Campuzano, V., Montermini, L., Moltò, M. D., Pianese, L., Cossée, M., Cavalcanti, F., Monros, E., Rodius, F., Duclos, F., Monticelli, A., et al. (1996) · Science · doi:10.1126/science.271.5254.1423 · Cited by 2,786
Selective Targeting of a Redox-active Ubiquinone to Mitochondria within Cells
Kelso, G. F., Porteous, C. M., Coulter, C. V., Hughes, G., Porteous, W. K., Ledgerwood, E. C., Smith, R. A. J., & Murphy, M. P. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m009093200 · Cited by 1,091
Self-citationRegulation of Mitochondrial Iron Accumulation by Yfh1p, a Putative Homolog of Frataxin
Babcock, M., de Silva, D., Oaks, R., Davis-Kaplan, S., Jiralerspong, S., Montermini, L., Pandolfo, M., & Kaplan, J. (1997) · Science · doi:10.1126/science.276.5319.1709 · Cited by 921
Puccio, H., Simon, D., Cossée, M., Criqui-Filipe, P., Tiziano, F., Melki, J., Hindelang, C., Matyas, R., Rustin, P., & Koenig, M. (2001) · Nature Genetics · doi:10.1038/84818 · Cited by 738
Delivery of bioactive molecules to mitochondria in vivo
Smith, R. A. J., Porteous, C. M., Gane, A. M., & Murphy, M. P. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0931245100 · Cited by 725
Self-citationSelective targeting of an antioxidant to mitochondria
Smith, R. A. J., Porteous, C. M., Coulter, C. V., & Murphy, M. P. (1999) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.1999.00543.x · Cited by 466
Self-citationDrug delivery to mitochondria: the key to mitochondrial medicine
Murphy, M. P., & Smith, R. A. J. (2000) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(99)00069-1 · Cited by 429
Self-citationSelective targeting of bioactive compounds to mitochondria
Murphy, M. P. (1997) · Trends in Biotechnology · doi:10.1016/s0167-7799(97)01068-8 · Cited by 366
Deficit of in vivo mitochondrial ATP production in patients with Friedreich ataxia
Lodi, R., Cooper, J. A. D., Bradley, J. L., Manners, D. N., Styles, P., Taylor, D. J., & Schapira, A. H. V. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.20.11492 · Cited by 352
Respiratory deficiency due to loss of mitochondrial DNA in yeast lacking the frataxin homologue
Wilson, R. B., & Roof, D. M. (1997) · Nature Genetics · doi:10.1038/ng0897-352 · Cited by 345
Oxidative stress in patients with Friedreich ataxia
Schulz, J. B., Dehmer, T., Schöls, L. J., Mende, H. E., Hardt, C., Vorgerd, M., Bürk, K., Matson, W. R., DICHGANS, J., Beal, M. F., et al. (2000) · Neurology · doi:10.1212/wnl.55.11.1719 · Cited by 305
Idebenone and reduced cardiac hypertrophy in Friedreich's ataxia
HAUSSE, A., Aggoun, Y., Bonnet, D., Sidi, D., Münnich, A., Rötig, A., & Rustin, P. (2002) · Heart · doi:10.1136/heart.87.4.346 · Cited by 251
Lodi, R., Hart, P. E., Rajagopalan, B., Taylor, D. J., Crilley, J. G., Bradley, J. L., Blamire, A. M., Manners, D. N., Styles, P., Schapira, A. H. V., et al. (2001) · Annals of Neurology · doi:10.1002/ana.1001 · Cited by 238
Altered mitochondrial function in fibroblasts containing MELAS or MERRF mitochondrial DNA mutations
James, A. M., Wei, Y., Pang, C., & Murphy, M. P. (1996) · Biochemical Journal · doi:10.1042/bj3180401 · Cited by 167
Recent advances in the molecular pathogenesis of Friedreich ataxia
Puccio, H. M. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.6.887 · Cited by 146
Prevention of Mitochondrial Oxidative Damage Using Targeted Antioxidants
Kelso, G. F., Porteous, C. M., Hughes, G., Ledgerwood, E. C., Gane, A. M., Smith, R. A. J., & Murphy, M. P. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb02098.x · Cited by 132
Self-citationFriedreich ataxia: a paradigm for mitochondrial diseases
Puccio, H. M., & Koenig, M. (2002) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(02)00298-8 · Cited by 111
Jauslin, M. L. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.24.3055 · Cited by 106
Self-citationDevelopment of lipophilic cations as therapies for disorders due to mitochondrial dysfunction
Murphy, M. P. (2001) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.1.5.753 · Cited by 76
Friedreich’s ataxia is a mitochondrial disorder
Kaplan, J. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.20.10948 · Cited by 38
Measurement of tumor necrosis factor activity by flow cytometry
Lévesque, A., Paquet, A., & Pagé, M. (1995) · Cytometry · doi:10.1002/cyto.990200211 · Cited by 23
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Bhatti, J. S., Bhatti, G. K., & Reddy, P. H. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.11.010 · Cited by 1,655
Trinucleotide Repeat Disorders
Orr, H. T., & Zoghbi, H. Y. (2007) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.29.051605.113042 · Cited by 1,394
Targeting Antioxidants to Mitochondria by Conjugation to Lipophilic Cations
Murphy, M. P., & Smith, R. A. J. (2007) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.47.120505.105110 · Cited by 1,173
Self-citationMitochondrial and metabolic dysfunction in ageing and age-related diseases
Amorim, J. A., Coppotelli, G., Rolo, A. P., Palmeira, C. M., Ross, J. M., & Sinclair, D. A. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00626-7 · Cited by 990
Zhao, K., Zhao, G.-M., Wu, D., Soong, Y., Birk, A. V., Schiller, P. W., & Szeto, H. H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m402999200 · Cited by 782
Metadata
- Authors
- Jauslin, M. L., Meier, T., Smith, R. A. J., & Murphy, P. M.
- Affiliations
- Geotech Co., Ltd. (Japan) (JP)
- University of Otago (NZ)
- MRC-Dunn Human Nutrition Unit Cambridge CB2 2XY United Kingdom
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2003-08-15
- Volume
- 17
- Issue
- 13
- Pages
- 1-10
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2154919554
- Cited by
- 358
- References
- 21
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 8 · 2023: 14 · 2022: 11 · 2021: 7 · 2020: 11 · 2019: 9 · 2018: 13 · 2017: 9 · 2016: 11 · 2015: 14 · 2014: 17 · 2013: 19 · 2012: 21
- FWCI
- 7.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Commission (QLRT-CT-1999-00584)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Keywords
- Friedreich's ataxia, mitochondria-targeted antioxidants, oxidative stress, frataxin, mitochondrial oxidative damage, MitoQ, idebenone, Trolox, vitamin E, coenzyme Q10, glutathione deficiency, fibroblasts, cell death, mitochondrial disease therapy
- MeSH terms
- Antioxidants, Fibroblasts, Friedreich Ataxia, Humans, Mitochondria, Models, Biological, Organophosphorus Compounds, Ubiquinone, Vitamin E, Benzoquinones, Drug Delivery Systems, Cell Death, Oxidative Stress
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