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• W2080109084 abstract "Alcohol treatment induces oxidative stress by a combination of increased production of partially reduced oxygen species and decreased cellular antioxidant pool, including GSH. Recently, we showed that mitochondrion-targeted CYP2E1 augments alcohol-mediated toxicity, causing an increase in reactive oxygen species production and oxidative stress. Here, we show that cytochrome c oxidase (CcO), the terminal oxidase of the mitochondrial respiratory chain, is a critical target of CYP2E1-mediated alcohol toxicity. COS-7 and Hep G2 cell lines expressing predominantly mitochondrion-targeted (Mt++) CYP2E1 and livers from alcohol-treated rats showed loss of CcO activity and increased protein carbonylation, which was accompanied by a decline in the steady state levels of subunits I, IVI1, and Vb of the CcO complex. This was also accompanied by reduced mitochondrial DNA content and reduced mitochondrial mRNA. These changes were more prominent in Mt++ cells in comparison with wild type (WT) CYP2E1-expressing or ER+ (mostly microsome-targeted) cells. In addition, mitochondrion-specific antioxidants, ubiquinol conjugated to triphenyl phosphonium, triphenylphosphonium conjugated carboxyl proxyl, and the CYP2E1 inhibitor diallyl sulfide prevented the loss of CcO activity and the CcO subunits, most likely through reduced oxidative damage to the enzyme complex. Our results suggest that damage to CcO and dissociation of respirosome complexes are critical factors in alcohol-induced toxicity, which is augmented by mitochondrion-targeted CYP2E1. We propose that CcO is one of the direct and immediate targets of alcohol-induced toxicity causing respiratory dysfunction. Alcohol treatment induces oxidative stress by a combination of increased production of partially reduced oxygen species and decreased cellular antioxidant pool, including GSH. Recently, we showed that mitochondrion-targeted CYP2E1 augments alcohol-mediated toxicity, causing an increase in reactive oxygen species production and oxidative stress. Here, we show that cytochrome c oxidase (CcO), the terminal oxidase of the mitochondrial respiratory chain, is a critical target of CYP2E1-mediated alcohol toxicity. COS-7 and Hep G2 cell lines expressing predominantly mitochondrion-targeted (Mt++) CYP2E1 and livers from alcohol-treated rats showed loss of CcO activity and increased protein carbonylation, which was accompanied by a decline in the steady state levels of subunits I, IVI1, and Vb of the CcO complex. This was also accompanied by reduced mitochondrial DNA content and reduced mitochondrial mRNA. These changes were more prominent in Mt++ cells in comparison with wild type (WT) CYP2E1-expressing or ER+ (mostly microsome-targeted) cells. In addition, mitochondrion-specific antioxidants, ubiquinol conjugated to triphenyl phosphonium, triphenylphosphonium conjugated carboxyl proxyl, and the CYP2E1 inhibitor diallyl sulfide prevented the loss of CcO activity and the CcO subunits, most likely through reduced oxidative damage to the enzyme complex. Our results suggest that damage to CcO and dissociation of respirosome complexes are critical factors in alcohol-induced toxicity, which is augmented by mitochondrion-targeted CYP2E1. We propose that CcO is one of the direct and immediate targets of alcohol-induced toxicity causing respiratory dysfunction." @default.
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• W2080109084 date "2012-05-01" @default.
• W2080109084 modified "2023-10-18" @default.
• W2080109084 title "Additive Effects of Mitochondrion-targeted Cytochrome CYP2E1 and Alcohol Toxicity on Cytochrome c Oxidase Function and Stability of Respirosome Complexes" @default.
• W2080109084 cites W12142967 @default.
• W2080109084 cites W1484442997 @default.
• W2080109084 cites W1541799695 @default.
• W2080109084 cites W1575711102 @default.
• W2080109084 cites W1650754258 @default.
• W2080109084 cites W1775749144 @default.
• W2080109084 cites W1966429519 @default.
• W2080109084 cites W1966512334 @default.
• W2080109084 cites W1966806720 @default.
• W2080109084 cites W1967251260 @default.
• W2080109084 cites W1972429510 @default.
• W2080109084 cites W1972534350 @default.
• W2080109084 cites W1974954009 @default.
• W2080109084 cites W1976505903 @default.
• W2080109084 cites W1977194186 @default.
• W2080109084 cites W1981280200 @default.
• W2080109084 cites W1984526747 @default.
• W2080109084 cites W1986918553 @default.
• W2080109084 cites W1990346327 @default.
• W2080109084 cites W1993137461 @default.
• W2080109084 cites W1995360843 @default.
• W2080109084 cites W1997611244 @default.
• W2080109084 cites W2000642498 @default.
• W2080109084 cites W2003803700 @default.
• W2080109084 cites W2005951306 @default.
• W2080109084 cites W2010524294 @default.
• W2080109084 cites W2010856194 @default.
• W2080109084 cites W2013161374 @default.
• W2080109084 cites W2015642381 @default.
• W2080109084 cites W2017267148 @default.
• W2080109084 cites W2019185659 @default.
• W2080109084 cites W2026383292 @default.
• W2080109084 cites W2028421665 @default.
• W2080109084 cites W2031118554 @default.
• W2080109084 cites W2032024781 @default.
• W2080109084 cites W2032678208 @default.
• W2080109084 cites W2032872396 @default.
• W2080109084 cites W2033522281 @default.
• W2080109084 cites W2033689665 @default.
• W2080109084 cites W2034711771 @default.
• W2080109084 cites W2034976767 @default.
• W2080109084 cites W2037804925 @default.
• W2080109084 cites W2037953589 @default.
• W2080109084 cites W2039579730 @default.
• W2080109084 cites W2040558033 @default.
• W2080109084 cites W2045003374 @default.
• W2080109084 cites W2049726232 @default.
• W2080109084 cites W2050688382 @default.
• W2080109084 cites W2053671179 @default.
• W2080109084 cites W2064176864 @default.
• W2080109084 cites W2068337326 @default.
• W2080109084 cites W2068799885 @default.
• W2080109084 cites W2073206349 @default.
• W2080109084 cites W2073642561 @default.
• W2080109084 cites W2076168953 @default.
• W2080109084 cites W2080265288 @default.
• W2080109084 cites W2080379235 @default.
• W2080109084 cites W2085101416 @default.
• W2080109084 cites W2090367343 @default.
• W2080109084 cites W2092165077 @default.
• W2080109084 cites W2093491167 @default.
• W2080109084 cites W2096764074 @default.
• W2080109084 cites W2097711783 @default.
• W2080109084 cites W2116300323 @default.
• W2080109084 cites W2138145189 @default.
• W2080109084 cites W2138780460 @default.
• W2080109084 cites W2140656258 @default.
• W2080109084 cites W2140695384 @default.
• W2080109084 cites W2142546630 @default.
• W2080109084 cites W2150419930 @default.
• W2080109084 cites W2151816056 @default.
• W2080109084 cites W2160470644 @default.
• W2080109084 cites W2162900517 @default.
• W2080109084 cites W2168208715 @default.
• W2080109084 cites W2171073549 @default.
• W2080109084 cites W2171810710 @default.
• W2080109084 cites W2275889189 @default.
• W2080109084 cites W86055756 @default.
• W2080109084 doi "https://doi.org/10.1074/jbc.m111.314062" @default.
• W2080109084 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3346148" @default.
• W2080109084 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22396533" @default.
• W2080109084 hasPublicationYear "2012" @default.
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