Mitochondrial Targeting of Electron Scavenging Antioxidants: Regulation of Selective Oxidation vs Random Chain Reactions

Details

• Personal Author:
  Arias AKS ; Bayir H ; Belikova NA ; Borisenko G ; Greenberger JS ; Ji J ; Jiang JF ; Kagan VE ; Klein-Seetharaman J ; Pitt BR ; Shvedova AA ; Stoyanovsky D ; Tungekar MA ; Tyurina YY ; Wipf P ; Yanamala N
• 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. [Description provided by NIOSH]
• Subjects:
  Biological Products Lipids Occupational Health Oxidants Safety
• Keywords:
  Apoptosis Author Keywords: Cytochrome C Biological-agents Biological-effects Cardiolipin Cellular-transport-mechanism Cytotoxic-effects Gramicidin Mitochondria MnSOD Molecular-biology Molecular-structure Nitroxides Oxidative-metabolism Oxidative-processes Peroxidation Phospholipids S-conjugates Triphenylphosphonium

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• ISSN:
  0169-409X
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  61
• Issue:
  14
• NIOSHTIC Number:
  nn:20036250
• Citation:
  Adv Drug Deliv Rev 2009 Nov; 61(14)(SI):1375-1385
• Contact Point Address:
  Valerian E. Kagan, Univ Pittsburgh, Dept Environm & Occupat Hlth, Ctr Free Radical & Antioxidant Hlth, BRIDG, 100 Technol Dr, Room 330, Pittsburgh, PA 15219
• Email:
  kagan@pitt.edu
• Federal Fiscal Year:
  2010
• Peer Reviewed:
  True
• Source Full Name:
  Advanced Drug Delivery Reviews
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:429312afb796f5a731f8cfcb20a5fdf9843ebdbfc0edb014e9cc233ebeec94673d453089e446a79b9e74f30952c99d53bd1b967bb28542d57ed8847ff79868eb
• Download URL:
  https://stacks.cdc.gov/view/cdc/187742/cdc_187742_DS1.pdf
• File Type:
  [PDF - 596.45 KB ]