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Mitochondrial targeting of electron scavenging antioxidants: Regulation of selective oxidation vs random chain reactions

Kagan, VE and Wipf, P and Stoyanovsky, D and Greenberger, JS and Borisenko, G and Belikova, NA and Yanamala, N and Samhan Arias, AK and Tungekar, MA and Jiang, J and Tyurina, YY and Ji, J and Klein-Seetharaman, J and Pitt, BR and Shvedova, AA and Bayir, H (2009) Mitochondrial targeting of electron scavenging antioxidants: Regulation of selective oxidation vs random chain reactions. Advanced Drug Delivery Reviews, 61 (14). 1375 - 1385. ISSN 0169-409X

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Effective regulation of highly compartmentalized production of reactive oxygen species and peroxidation reactions in mitochondria requires targeting of small molecule antioxidants and antioxidant enzymes into the organelles. This review describes recently developed approaches to mitochondrial targeting of small biologically active molecules based on: (i) preferential accumulation in mitochondria because of their hydrophobicity and positive charge (hydrophobic cations), (ii) binding with high affinity to an intra-mitochondrial constituent, and (iii) metabolic conversions by specific mitochondrial enzymes to reveal an active entity. In addition, targeted delivery of antioxidant enzymes via expression of leader sequences directing the proteins into mitochondria is considered. Examples of successful antioxidant and anti-apoptotic protection based on the ability of targeted cargoes to inhibit cytochrome c-catalyzed peroxidation of a mitochondria-specific phospholipid cardiolipin, in vitro and in vivo are presented. Particular emphasis is placed on the employment of triphenylphosphonium- and hemi-gramicidin S-moieties as two effective vehicles for mitochondrial delivery of antioxidants. © 2009 Elsevier B.V. All rights reserved.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Kagan, VEkagan@pitt.eduKAGAN
Wipf, Ppwipf@pitt.eduPWIPF
Stoyanovsky, Ddas11@pitt.eduDAS110000-0001-5591-4780
Greenberger, JSjoelg@pitt.eduJOELG
Borisenko, G
Belikova, NA
Yanamala, N
Samhan Arias, AK
Tungekar, MA
Jiang, Jjjf73@pitt.eduJJF73
Tyurina, YY
Ji, J
Klein-Seetharaman, J
Pitt, BRbrucep@pitt.eduBRUCEP
Shvedova, AA
Bayir, Hhub22@pitt.eduHUB220000-0003-2361-4120
Date: 30 November 2009
Date Type: Publication
Journal or Publication Title: Advanced Drug Delivery Reviews
Volume: 61
Number: 14
Page Range: 1375 - 1385
DOI or Unique Handle: 10.1016/j.addr.2009.06.008
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Refereed: Yes
ISSN: 0169-409X
Article Type: Review
MeSH Headings: Animals; Antioxidants--pharmacology; Apoptosis--drug effects; Drug Delivery Systems--methods; Electron Transport Complex I--metabolism; Free Radical Scavengers--chemistry; Free Radical Scavengers--pharmacokinetics; Humans; Mitochondria--drug effects; Mitochondria--metabolism; Models, Biological; Molecular Structure; Oxidation-Reduction--drug effects; Oxidative Stress--drug effects; Reactive Oxygen Species--metabolism
Other ID: NLM NIHMS142023, NLM PMC2784017
PubMed Central ID: PMC2784017
PubMed ID: 19716396
Date Deposited: 07 Jun 2013 20:42
Last Modified: 16 Sep 2020 13:55


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