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How to Clean the Dirtiest Place in the Cell: Cationic Antioxidants as Intramitochondrial ROS Scavengers
Author(s) -
Skulachev Vladimir P.
Publication year - 2005
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/15216540500092161
Subject(s) - mitochondrion , reactive oxygen species , chemistry , membrane potential , ubiquinol , inner mitochondrial membrane , apoptosis , biophysics , biochemistry , biology , coenzyme q – cytochrome c reductase , cytochrome c
Abstract Membrane‐penetrating triphenyl alkyl phosphonium cations have been suggested for many years in our group as having the ability to measure mitochondrial potential were recently used by Murphy as vehicles to specifically target CoQ to mitochondria. As was shown in our group, the phosphonium derivative of CoQ (MitoQ) easily penetrates a planar bilayer phospholipid membrane as a cation, generating 60 mV electric potential (ΔΨ) per a 10‐fold MitoQ gradient. This means that MitoQ should be unequally distributed across the inner mitochondrial membrane, the intramitochondrial [MitoQ] = extramitochondrial [MitoQ] × 103 at 180 mV ΔΨ. In line with such a calculation, Murphy and his colleagues reported that antioxidant efficiency of MitoQ added to mitochondria or cells appears to be very much higher than of CoQ. It was found that H2O2‐induced apoptosis (Murphy) and the H2O2‐mediated bystander killing of the cultivated cells (our group) are completely arrested by pretreatement of the cells with 10‐10 ‐ 10‐8 M MitoQ. These effects indicate that MitoQ and similar compounds may be promising in treatment of heart attack, stroke and other diseases accompanied by massive apoptosis in the injured tissue. The very fact that: (i) MitoQ is not only accumulated by mitochondria but also can be regenerated in its reduced form by mitochondrial respiratory chain, (ii) it is the mitochondrial interior that produces a large portion of reactive oxygen species (ROS) in our body, and (iii) the most sensitive ROS targets are localized in the mitochondrial matrix suggest the MitoQ‐like compounds are promising tools of molecular therapy of aerobic cells. In line with this suggestion, we found that addition of MitoQ strongly improves structural and biochemical parameters of cultivated cells. As to cationic tetrapeptides, recently advertised as mitochondrially‐targeted ΔΨ ‐independent antioxidants, their effect is most probably mediated by an opioid activity inherent in some of these substances.IUBMB Life, 57: 305‐310, 2005