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Cited by 121Mitochondrial Function and PathologyNeuroprotection in Cerebral IschemiaNanoparticle-Based Drug Delivery

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

Porteous, Carolyn M., Logan, Angela, Evans, Cameron, Ledgerwood, Elizabeth C., Menon, David K., Aigbirhio, Franklin, Smith, Robin A.J., Murphy, Michael P.·2010·Biochimica et Biophysica Acta (BBA) - General Subjects
DOI 10.1016/j.bbagen.2010.06.001
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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.

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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.
ORCID
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)
DOI
10.1016/j.bbagen.2010.06.001
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

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