relation: http://d-scholarship-dev.library.pitt.edu/18829/
title: Mitochondrial targeting of electron scavenging antioxidants: Regulation of selective oxidation vs random chain reactions
creator: Kagan, VE
creator: Wipf, P
creator: Stoyanovsky, D
creator: Greenberger, JS
creator: Borisenko, G
creator: Belikova, NA
creator: Yanamala, N
creator: Samhan Arias, AK
creator: Tungekar, MA
creator: Jiang, J
creator: Tyurina, YY
creator: Ji, J
creator: Klein-Seetharaman, J
creator: Pitt, BR
creator: Shvedova, AA
creator: Bayir, H
description: 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.
date: 2009-11-30
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/18829/1/licence.txt
identifier:   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     
relation: 10.1016/j.addr.2009.06.008