title: Cellular and Molecular Mechanisms of Action of Mitochondria-Targeted Antioxidants.
abstract: Reactive oxygen species generated in mitochondria are an important factor contributing to mitochondrial and cellular dysfunction underlying many degenerative diseases, chronic pathologies and aging. The idea of delivering antioxidant molecules to mitochondria in vivo to treat these diseases and slow aging intensively developed in the last 20 years. Derivatives of quinones covalently conjugated to a lipophilic cation (e.g., MitoQ and SkQ) were the most extensively studied mitochondria-targeted antioxidants. These compounds have now been used in a wide range of in vitro and in vivo studies, as well as in clinical trials in humans. Here, we review recent progress in this field with a special attention on molecular mechanisms of rechargeable mitochondria-targeted antioxidants. A simple hypothesis that aging results from gradual accumulation of occasional damage inflicted by ROS to DNA, proteins and lipids is apparently insufficient. More and more pieces of evidence indicate that the damage in question is programmed. Moreover, the imbalance in ROS-dependent regulatory mechanisms and compromised ROS signaling are underlying many pathologies and aging. Chain reactions of cardiolipin peroxidation initiated by mitochondrial ROS seem to play a key role in these degenerative processes. Such reactions are specifically abolished by mitochondriatargeted antioxidants.
authors.forename: Boris A
authors.initials: BA
authors.lastname: Feniouk
authors.affiliation: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, GSP-1, Leninskiye Gory, Moscow, 119991, Russia.
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Skulachev
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D002308:Cardiolipins / Q000378:metabolism / Q000494:pharmacology; D019610:Cytoprotection / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D009589:Nitrogen Oxides / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002308:Cardiolipins; D016166:Free Radical Scavengers; D009589:Nitrogen Oxides; D017382:Reactive Oxygen Species