The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
Targeting an antioxidant to mitochondria decreases cardiac ischemia-reperfusion injury
Abstract
Mitochondrial oxidative damage contributes to a wide range of pathologies, including cardiovascular disorders and neurodegenerative diseases. Therefore, protecting mitochondria from oxidative damage should be an effective therapeutic strategy. However, conventional antioxidants have limited efficacy due to the difficulty of delivering them to mitochondria in situ. To overcome this problem, we developed mitochondria‐targeted antioxidants, typified by MitoQ, which comprises a lipophilic triphenylphosphonium (TPP) cation covalently attached to a ubiquinol antioxidant. Driven by the large mitochondrial membrane potential, the TPP cation concentrates MitoQ several hundred‐fold within mitochondria, selectively preventing mitochondrial oxidative damage. To test whether MitoQ was active in vivo, we chose a clinically relevant form of mitochondrial oxidative damage: cardiac ischemia‐reperfusion injury. Feeding MitoQ to rats significantly decreased heart dysfunction, cell death, and mitochondrial damage after ischemia‐reperfusion. This protection was due to the antioxidant activity of MitoQ within mitochondria, as an untargeted antioxidant was ineffective and accumulation of the TPP cation alone gave no protection. Therefore, targeting antioxidants to mitochondria in vivo is a promising new therapeutic strategy in the wide range of human diseases such as Parkinson's disease, diabetes, and Friedreich's ataxia where mitochondrial oxidative damage underlies the pathology. Adlam, V. J., Harrison, J. C., Porteous, C. M., James, A. M., Smith, R. A. J., Murphy, M. P., Sammut, I. A. Targeting an antioxidant to mitochondria decreases cardiac ischemia‐reperfusion injury. FASEB J. 19, 1088–1095 (2005)
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“For example, Mitoquinone (MitoQ) has been tested successfully in human diseases such as Hepatitis C induced liver disease and skin photo damage as well as a number of experimental animal models including ischemia-reperfusion, neurodegenerative diseases, diabetes, and alcohol-induced hepatosteatosis [8–14].”
From Mitochondrially targeted compounds and their impact on cellular bioenergetics (2013) · cites this paper as [10]
In the citing paper
“A number of studies show that, when MitoQ is administered to in vivo animal models of pathologies, it reduces both oxidative damage and the pathologies (Adlam et al., 2005; Lowes et al., 2008; Graham et al., 2009; Supinski et al., 2009; Chacko et al., 2010; Smith and Murphy 2010).”
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 Adlam et al., 2005
Citations
Cites
PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT
Lowry, O. H., Rosebrough, N., Farr, A. L., & Randall, R. (1951) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)52451-6 · Cited by 316,394
(1975) · Journal of AOAC INTERNATIONAL · doi:10.1093/jaoac/58.5.1085 · Cited by 20,078
Beckman, J. S., Beckman, T. W., Chen, J., Marshall, P. A., & Freeman, B. A. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.4.1620 · Cited by 7,029
Mitochondrial diseases in man and mouse
Wallace, D. C. (1999) · Science · doi:10.1126/science.283.5407.1482 · Cited by 3,060
Holbrook, J. J., Liljas, A., Steindel, S. J., & Rossmann, M. G. (1975) · The Enzymes · doi:10.1016/s1874-6047(08)60212-7 · Cited by 1,248
Direct measurement of free radical generation following reperfusion of ischemic myocardium.
Zweier, J. L., Flaherty, J. T., & Weisfeldt, M. L. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.5.1404 · Cited by 1,189
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-citationMitochondria, oxygen free radicals, disease and ageing
Raha, S., & Robinson, B. H. (2000) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)01674-1 · Cited by 1,066
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-citationUV-Assay with Pyruvate and NADH
Bergmeyer, H. U., & Bernt, E. (1974) · Elsevier eBooks · doi:10.1016/b978-0-12-091302-2.50010-4 · Cited by 617
Role of the Mitochondrial Permeability Transition in Myocardial Disease
Weiss, J. N., Kôrge, P., Honda, H. M., & Ping, P. (2003) · Circulation Research · doi:10.1161/01.res.0000087542.26971.d4 · Cited by 610
Paradies, G., Petrosillo, G., Pistolese, M., Di Venosa, N., Federici, A., & Ruggiero, F. M. (2004) · Circulation Research · doi:10.1161/01.res.0000109416.56608.64 · Cited by 468
Drug 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-citationThe role of iron in the activation-inactivation of aconitase.
Kennedy, M. C., Emptage, M. H., Dreyer, J.-L., & Beinert, H. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)44390-0 · Cited by 377
Selective targeting of bioactive compounds to mitochondria
Murphy, M. P. (1997) · Trends in Biotechnology · doi:10.1016/s0167-7799(97)01068-8 · Cited by 366
Self-citationJauslin, M. L., Meier, T., Smith, R. A. J., & Murphy, P. M. (2003) · The FASEB Journal · doi:10.1096/fj.03-0240fje · Cited by 358
Self-citationOverexpression of MnSOD Protects Against Myocardial Ischemia/reperfusion Injury in Transgenic Mice
Chen, Z., Siu, B., Ho, Y., Vincent, R., Chua, C. C., Hamdy, R. C., & Chua, B. H. L. (1998) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.1998.0789 · Cited by 346
Conversion of biomembrane-produced energy into electric form. I. Submitochondrial particles
Grinius, L., JASAITIS, A. A., Kadziauskas, Y. P., Liberman, E. A., Skulachev, V. P., Vp, T., Tsofina, L. M., & Vladimirova, M. A. (1970) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(70)90153-2 · Cited by 324
Mitochondrial Aconitase Is a Source of Hydroxyl Radical
Vasquez-Vivar, J. M., Kalyanaraman, B., & Kennedy, M. C. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.19.14064 · Cited by 317
Dhanasekaran, A., Kotamraju, S., Kalivendi, S. V., Matsunaga, T., Shang, T., Keszler, A., Joseph, J., & Kalyanaraman, B. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m404003200 · Cited by 241
Borutaitė, V. (2003) · Journal of Molecular and Cellular Cardiology · doi:10.1016/s0022-2828(03)00005-1 · Cited by 203
Fine-tuning the hydrophobicity of a mitochondria-targeted antioxidant
Asin-Cayuela, J., Manas, A.-R. B., James, A. M., Smith, R. A. J., & Murphy, M. P. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.06.045 · Cited by 184
Self-citationAltered 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
Self-citationAntioxidants in myocardial ischemia–reperfusion injury: therapeutic potential and basic mechanisms
Marczin, N., El-Habashi, N., Hoare, G. S., Bundy, R. E., & Yacoub, M. H. (2003) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2003.08.037 · Cited by 165
Suzuki, K., Murtuza, B., Sammut, I. A., Latif, N., Jayakumar, J., Smolenski, R. T., Kaneda, Y., Sawa, Y., Matsuda, H., & Yacoub, M. H. (2002) · Circulation · doi:10.1161/01.cir.0000032880.55215.92 · Cited by 147
Self-citationPrevention 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-citationPostischemic Recovery of Contractile Function is Impaired in SOD2 +/− but Not SOD1 +/− Mouse Hearts
Asimakis, G. K., Lick, S. D., & Patterson, C. (2002) · Circulation · doi:10.1161/hc0802.104502 · Cited by 125
Hardy, L., Clark, J. B., Darley-Usmar, V. M., Smith, D. R., & Stone, D. (1991) · Biochemical Journal · doi:10.1042/bj2740133 · Cited by 123
Ischemia–reperfusion injury in the aged heart: role of mitochondria
Lesnefsky, E. J., & Hoppel, C. L. (2003) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2003.09.046 · Cited by 122
Lifespan and mitochondrial control of neurodegeneration
Wright, A. F., Jacobson, S. G., Cideciyan, A. V., Roman, A. J., Shu, X., Vlachantoni, D., McInnes, R. R., & Riemersma, R. A. (2004) · Nature Genetics · doi:10.1038/ng1448 · Cited by 111
Borutaitė, V., Jekabsone, A., Morkūnienė, R., & Brown, G. C. (2001) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/s0925-4439(01)00062-x · Cited by 97
Mitochondria. A practical approach
McCormack, J. (1988) · Biochemical Education · doi:10.1016/0307-4412(88)90107-0 · Cited by 95
Heat Stress Contributes to the Enhancement of Cardiac Mitochondrial Complex Activity
Sammut, I. A., Jayakumar, J., Latif, N., ROTHERY, S. M., Severs, N. J., Smolenski, R. T., Bates, T. E., & Yacoub, M. H. (2001) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64138-7 · Cited by 92
Self-citationClarkson, A. N., Liu, H., Pearson, L., Kapoor, M., Harrison, J. C., Sammut, I. A., Jackson, D. M., & Appleton, I. (2004) · The FASEB Journal · doi:10.1096/fj.03-1203fje · Cited by 71
Self-citationMurphy, M. P. (2001) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(00)00234-6 · Cited by 56
Self-citationWater content and its intracellular distribution in intact and saline perfused rat hearts revisited
Aliev, M. (2002) · Cardiovascular Research · doi:10.1016/s0008-6363(01)00474-6 · Cited by 55
Cardiac ischemia/reperfusion, aging, and redox-dependent alterations in mitochondrial function
Sadek, H. A., Nulton-Persson, A. C., Szweda, P. A., & Szweda, L. I. (2003) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2003.09.029 · Cited by 52
OKAMOTO, K., MATSUMOTO, M., Watanabe, M., Kawada, M., Imamoto, T., & Imada, I. (1985) · Chemical and Pharmaceutical Bulletin · doi:10.1248/cpb.33.3745 · Cited by 41
Mitochondrial membrane potentials in ischemic hearts
Berkich, D. A., Salama, G., & LaNoue, K. F. (2003) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2003.09.021 · Cited by 34
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Powers, S. K., & Jackson, M. J. (2008) · Physiological Reviews · doi:10.1152/physrev.00031.2007 · Cited by 2,459
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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
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Metadata
- Authors
- Adlam, V. J., Harrison, J. C., Porteous, C. M., James, A. M., Smith, R. A. J., Murphy, M. P., & Sammut, I. A.
- Affiliations
- University of Otago (NZ)
- MRC Mitochondrial Biology Unit (GB)
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2005-07
- Volume
- 19
- Issue
- 9
- Pages
- 1088-1095
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2060179384
- Semantic Scholar
- 7c4097d1a1a2771b393d479d8b5d4e5cf4eeeacb
- Cited by
- 618
- References
- 39
- Citations by year
- 2026: 10 · 2025: 26 · 2024: 11 · 2023: 17 · 2022: 28 · 2021: 28 · 2020: 38 · 2019: 36 · 2018: 32 · 2017: 25 · 2016: 32 · 2015: 40 · 2014: 45 · 2013: 33 · 2012: 34
- FWCI
- 19.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Ischemia and Reperfusion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Neuroscience › Neurology › Neuroprotection in Cerebral Ischemia
- Keywords
- mitochondria-targeted antioxidants, MitoQ, myocardial ischemia-reperfusion injury, mitochondrial oxidative damage, triphenylphosphonium cation, ubiquinol, mitochondrial membrane potential, cardiac dysfunction, mitochondrial cell death, Parkinson's disease, Friedreich's ataxia, diabetes mellitus
- MeSH terms
- Animals, Antioxidants, Heart, Male, Mitochondria, Organophosphorus Compounds, Oxygen Consumption, Ubiquinone, Myocardial Reperfusion Injury, Rats, Wistar, Protective Agents, Cytochromes c, Rats
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