The DOI matches its Crossref record; 52 of the 55 references it cites were found in a registry or an index.
Rapid uptake of lipophilic triphenylphosphonium cations by mitochondria in vivo following intravenous injection: Implications for mitochondria-specific therapies and probes
Abstract
Background Mitochondrial dysfunction contributes to a range of pathologies, consequently there is a need to monitor mitochondrial function and to intervene pharmacologically to prevent mitochondrial damage. One approach to this is to deliver antioxidants, probes and pharmacophores to mitochondria by conjugation to the lipophilic triphenylphosphonium (TPP) cation that is taken up selectively by mitochondria driven by the membrane potential.Conclusions Oral administration of TPP-conjugated antioxidants protects against mitochondrial damage in vivo. However, there is also a need to deliver molecules rapidly to mitochondria to respond quickly to pathologies and for the real-time assessment of mitochondrial function.Methods To see if this was possible we investigated how rapidly TPP cations were taken up by mitochondria in vivo following intravenous (iv) administration.Results AlkylTPP cations were accumulated selectively by mitochondria within mice within 5 min of iv injection. The extent of uptake was enhanced 10-30-fold relative to simple alkylTPP cations by attaching functional groups to the TPP cation via long, hydrophobic alkyl chains. Conclusions: Mitochondria-targeted antioxidants, probes and pharmacophores can be delivered into mitochondria within minutes of iv administration.General significance These findings greatly extend the utility of mitochondria-targeted lipophilic cations as therapies and probes.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“As triphenylphosphonium cations drive accumulation within cardiac mitochondria within minutes of intravenous administration14”
From Cardioprotection by S-nitrosation of a cysteine switch on mitochondrial complex I (2013) · cites this paper as [14]
Citations
Cites
Measurement of protein using bicinchoninic acid
Smith, P. K., Krohn, R. I., Hermanson, G. T., Mallia, A. K., Gartner, F. H., Provenzano, M. D., Fujimoto, E. K., Goeke, N. M., Olson, B. J., & Klenk, D. C. (1985) · Analytical Biochemistry · doi:10.1016/0003-2697(85)90442-7 · Cited by 18,482
Effect of Cyclosporine on Reperfusion Injury in Acute Myocardial Infarction
Piot, C. A., Croisille, P., Staat, P., Thibault, H., Rioufol, G., Mewton, N., Belghiti, R. E., Cung, T. T., Bonnefoy‐Cudraz, E., Angoulvant, D., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa071142 · Cited by 1,339
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-citationSelective 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-citationMitochondrial Membrane Potential in Living Cells
Chen, L. B. (1988) · Annual Review of Cell Biology · doi:10.1146/annurev.cb.04.110188.001103 · Cited by 1,039
Selective fluorescent imaging of superoxide in vivo using ethidium-based probes
Robinson, K. M., Janes, M. S., Pehar, M., Monette, J. S., Ross, M. F., Hagen, T. M., Murphy, M. P., & Beckman, J. S. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601945103 · Cited by 777
Self-citationDelivery 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-citationA Targetable Fluorescent Probe for Imaging Hydrogen Peroxide in the Mitochondria of Living Cells
Dickinson, B. C., & Chang, C. J. (2008) · Journal of the American Chemical Society · doi:10.1021/ja802355u · Cited by 646
Targeting an antioxidant to mitochondria decreases cardiac ischemia-reperfusion injury
Adlam, V. J., Harrison, J. C., Porteous, C. M., James, A. M., Smith, R. A. J., Murphy, M. P., & Sammut, I. A. (2005) · The FASEB Journal · doi:10.1096/fj.05-3718com · Cited by 618
Self-citationSnow, B. J., Rolfe, F. L., Lockhart, M. M., Frampton, C. M., O'Sullivan, J. D., Fung, V., Smith, R. A. J., Murphy, M. P., Taylor, K. M., & On behalf of the Protect Study Group (2010) · Movement Disorders · doi:10.1002/mds.23148 · Cited by 606
Self-citationRoss, M. F., Kelso, G. F., Blaikie, F. H., James, A. M., Cochemé, H. M., Filipovska, A., Ros, T. D., Hurd, T. R., Smith, R. A. J., & Murphy, M. P. (2005) · Biochemistry (Moscow) · doi:10.1007/s10541-005-0104-5 · Cited by 504
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-citationSubcellular components: preparation and fractionation;
Birnie, G. D. (1972) · Cited by 422
Gane, E. J., Weilert, F., Orr, D. W., Keogh, G. F., Gibson, M., Lockhart, M. M., Frampton, C. M., Taylor, K. M., Smith, R. A. J., & Murphy, M. P. (2010) · Liver International · doi:10.1111/j.1478-3231.2010.02250.x · Cited by 379
Self-citationGraham, D., Huynh, N. N., Hamilton, C. A., Beattie, E., Smith, R. A. J., Cochemé, H. M., Murphy, M. P., & Dominiczak, A. F. (2009) · Hypertension · doi:10.1161/hypertensionaha.109.130351 · Cited by 367
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
Self-citationJames, A. M., Cochemé, H. M., Smith, R. A. J., & Murphy, M. P. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501527200 · Cited by 353
Self-citationMurphy, M. P., Echtay, K. S., Blaikie, F. H., Asin-Cayuela, J., Cochemé, H. M., Green, K., Buckingham, J. A., Taylor, E. R., Hurrell, F., Hughes, G., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m308529200 · Cited by 313
Self-citationLowes, D. A., Thottakam, B. M. V., Webster, N. R., Murphy, M. P., & Galley, H. F. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.09.003 · Cited by 261
Self-citationPrime, T. A., Blaikie, F. H., Evans, C., Nadtochiy, S. M., James, A. M., Dahm, C. C., Vitturi, D. A., Patel, R. P., Hiley, C. R., Abakumova, I., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903250106 · Cited by 222
Self-citationRodriguez-Cuenca, S., Cochemé, H. M., Logan, A., Abakumova, I., Prime, T. A., Rose, C., Vidal-Puig, A., Smith, A. C., Rubinsztein, D. C., Fearnley, I. M., et al. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.10.039 · Cited by 218
Self-citationRapid and extensive uptake and activation of hydrophobic triphenylphosphonium cations within cells
Ross, M. F., Prime, T. A., Abakumova, I., James, A. M., Porteous, C. M., Smith, R. A. J., & Murphy, M. P. (2008) · Biochemical Journal · doi:10.1042/bj20080063 · Cited by 206
Self-citationDhanasekaran, A., Kotamraju, S., Karunakaran, C., Kalivendi, S. V., Thomas, S., Joseph, J., & Kalyanaraman, B. (2005) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.04.016 · Cited by 193
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-citationSpecific Modification of Mitochondrial Protein Thiols in Response to Oxidative Stress
Lin, T., Hughes, G., Muratovska, A., Blaikie, F. H., Brookes, P. S., Darley-Usmar, V. M., Smith, R. A. J., & Murphy, M. P. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m110797200 · Cited by 180
Self-citationDoxorubicin Inactivates Myocardial Cytochrome c Oxidase in Rats: Cardioprotection by Mito-Q
Chandran, K., Aggarwal, D., Migrino, R. Q., Joseph, J., McAllister, D. M., Konorev, E. A., Antholine, W. E., Zielonka, J., Srinivasan, S., Avadhani, N. G., et al. (2009) · Biophysical Journal · doi:10.1016/j.bpj.2008.10.042 · Cited by 171
PREPARATION OF MITOCHONDRIA FROM ANIMAL TISSUES AND YEASTS
Chappell, J., & Hansford, R. G. (1972) · Elsevier eBooks · doi:10.1016/b978-0-408-70360-4.50009-2 · Cited by 141
Pandya, J. D., Pauly, J. R., Nukala, V. N., Sebastian, A. H., Day, K. M., Korde, A. S., Maragos, W. F., Hall, E. D., & Sullivan, P. G. (2007) · Journal of Neurotrauma · doi:10.1089/neu.2006.3673 · Cited by 130
Korde, A. S., Pettigrew, L. C., Craddock, S. D., & Maragos, W. F. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03328.x · Cited by 126
Accumulation of lipophilic dications by mitochondria and cells
Ross, M. F., Ros, T. D., Blaikie, F. H., Prime, T. A., Porteous, C. M., Severina, I. I., Skulachev, V. P., Kjaergaard, H. G., Smith, R. A. J., & Murphy, M. P. (2006) · Biochemical Journal · doi:10.1042/bj20060919 · Cited by 125
Self-citationMadar, I., Ravert, H. T., Du, Y., Hilton, J., Volokh, L., Dannals, R. F., Frost, J. J., & Hare, J. M. (2006) · PubMed · Cited by 115
Burns, R. J., Smith, R. A. J., & Murphy, M. P. (1995) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1995.1436 · Cited by 114
Self-citationComplex I Dysfunction and Tolerance to Nitroglycerin
Esplugues, J. V., Rocha, M., Nuñez, C., Boscá, I., Ibiza, S., Herance, J. R., Ortega, Á., Serrador, J. M., D’Ocón, P., & Víctor, V. M. (2006) · Circulation Research · doi:10.1161/01.res.0000250430.62775.99 · Cited by 103
Ross, M. F., Filipovska, A., Smith, R. A. J., Gait, M. J., & Murphy, M. P. (2004) · Biochemical Journal · doi:10.1042/bj20041095 · Cited by 94
Self-citationNeužil, J., Widén, C., Gellert, N., Swettenham, E., Zobalová, R., Dong, L., Wang, X., Lidebjer, C., Dalen, H., Headrick, J. P., et al. (2007) · Redox Report · doi:10.1179/135100007x200227 · Cited by 91
Targeting coenzyme Q derivatives to mitochondria
Smith, R. A. J., Kelso, G. F., James, A. M., & Murphy, M. P. (2004) · Methods in Enzymology · doi:10.1016/s0076-6879(04)82003-2 · Cited by 87
Self-citationHydrated Tetrabutylammonium Fluoride as a Powerful Nucleophilic Fluorinating Agent
Albanese, D. C. M., Landini, D., & Penso, M. (1998) · The Journal of Organic Chemistry · doi:10.1021/jo981522o · Cited by 82
Plotnikov, E. Y., Vasileva, A. K., Arkhangelskaya, A. A., Pevzner, I. B., Skulachev, V. P., & Zorov, D. B. (2008) · FEBS Letters · doi:10.1016/j.febslet.2008.08.002 · Cited by 66
Detection, Characterization, and Decay Kinetics of ROS and Thiyl Adducts of Mito-DEPMPO Spin Trap
Hardy, M., Rockenbauer, A., Vasquez-Vivar, J. M., Felix, C. C., López, M., Srinivasan, S., Avadhani, N. G., Tordo, P., & Kalyanaraman, B. (2007) · Chemical Research in Toxicology · doi:10.1021/tx700101d · Cited by 62
Toxic Fluorine Compounds. III.1 ι-Fluoroalcohols
Pattison, F. L. M., Howell, W. C., Mcnamara, A. J., SCHNEIDER, J. C., & Walker, J. F. (1956) · The Journal of Organic Chemistry · doi:10.1021/jo01113a006 · Cited by 57
Manetta, A., Gamboa, G., Nasseri, A., Podnos, Y. D., Emma, D., Dorion, G. E., Rawlings, L., Carpenter, P. M., Bustamante, A., Patel, J., et al. (1996) · Gynecologic Oncology · doi:10.1006/gyno.1996.0026 · Cited by 53
Hardy, M., Chalier, F., Ouari, O., Finet, J., Rockenbauer, A., Kalyanaraman, B., & Tordo, P. (2007) · Chemical Communications · doi:10.1039/b616076j · Cited by 48
Chemoselective fluorination for primary alcohols
Shimizu, M., Nakahara, Y., & Yoshioka, H. (1985) · Tetrahedron Letters · doi:10.1016/s0040-4039(00)98993-7 · Cited by 44
Xu, Y., & Kalyanaraman, B. (2006) · Free Radical Research · doi:10.1080/10715760600911147 · Cited by 43
Enhanced uptake of [11C]TPMP in canine brain tumor: a PET study.
Madar, I., Anderson, J. H., Szabó, Z. R., Scheffel, U., Kao, P. F., Ravert, H. T., & Dannals, R. F. (1999) · PubMed · Cited by 34
Korde, A. S., Sullivan, P. G., & Maragos, W. F. (2005) · Journal of Neurotrauma · doi:10.1089/neu.2005.22.1142 · Cited by 32
Specific targeting of a DNA‐alkylating reagent to mitochondria
James, A. M., Blaikie, F. H., Smith, R. A. J., Lightowlers, R. N., Smith, P., & Murphy, M. P. (2003) · European Journal of Biochemistry · doi:10.1046/j.1432-1033.2003.03660.x · Cited by 24
Self-citationLi, Y., Zhang, H., Fawcett, J. P., & Tucker, I. G. (2007) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.3048 · Cited by 24
Patel, J., Rideout, D. C., McCarthy, M. R., Calogeropoulou, T., Wadwa, K. S., & Oseroff, A. R. (1994) · PubMed · Cited by 21
Effects of phosphonium compounds on Schistosoma mansoni
McAllister, P. R., Dotson, M. J., Grim, S. O., & Hillman, G. R. (1980) · Journal of Medicinal Chemistry · doi:10.1021/jm00182a010 · Cited by 19
Trujillo, J. G., Ceballos, G. M., Yañez, R., & Joseph‐Nathan, P. (1991) · Synthetic Communications · doi:10.1080/00397919108020837 · Cited by 9
Cited by
Sorted by citations
Zielonka, J., Joseph, J., Sikora, A., Hardy, M., Ouari, O., Vasquez-Vivar, J., Cheng, G., Lopez, M., & Kalyanaraman, B. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00042 · Cited by 1,683
Cardioprotection by S-nitrosation of a cysteine switch on mitochondrial complex I
Chouchani, E. T., Methner, C., Nadtochiy, S. M., Logan, A., Pell, V. R., Ding, S., James, A. M., Cochemé, H. M., Reinhold, J., Lilley, K. S., et al. (2013) · Nature Medicine · doi:10.1038/nm.3212 · Cited by 619
Self-citationSmith, R. A. J., Hartley, R. C., Cochemé, H. M., & Murphy, M. P. (2012) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2012.03.010 · Cited by 514
Self-citationZhang, W., Hu, X., Shen, Q., & Xing, D. (2019) · Nature Communications · doi:10.1038/s41467-019-09566-3 · Cited by 446
Mitochondria-Targeted Small Molecule Therapeutics and Probes
Smith, R. A. J., Hartley, R. C., & Murphy, M. P. (2011) · Antioxidants & Redox Signaling · doi:10.1089/ars.2011.3969 · Cited by 399
Self-citation
Metadata
- Authors
- Porteous, C. M., Logan, A., Evans, C., Ledgerwood, E. C., Menon, D. K., Aigbirhio, F., Smith, R. A. J., & Murphy, M. P.
- Affiliations
- University of Otago (NZ)
- MRC Mitochondrial Biology Unit (GB)
- University of Cambridge (GB)
- Corresponding author
- Murphy, Michael P.
- Venue
- Biochimica et Biophysica Acta (BBA) - General Subjects
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 1800
- Issue
- 9
- Pages
- 1009-1017
- ISSN
- 0304-4165 (ISSN-L)
- OpenAlex
- W1971782930
- Cited by
- 121
- References
- 55
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 1 · 2023: 4 · 2022: 9 · 2021: 8 · 2020: 7 · 2019: 10 · 2018: 6 · 2017: 12 · 2016: 7 · 2015: 7 · 2014: 12 · 2013: 11 · 2012: 9
- FWCI
- 3.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - General Subjects (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute for Health Research
- Asia New Zealand Foundation
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Neuroscience › Neurology › Neuroprotection in Cerebral Ischemia
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- triphenylphosphonium cation, mitochondrial membrane potential, mitochondrial uptake, mitochondria-targeted antioxidants, hydrophobic alkyl chains, mitochondrial dysfunction, mitochondrial damage, intravenous administration
- MeSH terms
- Animals, Antioxidants, Cations, Female, Injections, Intravenous, Mitochondria, Organophosphorus Compounds, Drug Delivery Systems, Mitochondrial Diseases, Mice, Membrane Potential, Mitochondrial
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
