Opposite and tissue-specific effects of coenzyme Q₂ on mPTP opening and ROS production between heart and liver mitochondria: Role of complex I

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• 作者：Abdallah Gharib^a ; ^{abdallah.gharib@univ-lyon1.fr} ; Damien De Paulis^a ; ^b ; Bo Li^a ; ^b ; Lionel Augeul^a ; ^b ; Elisabeth Couture-Lepetit^a ; ^b ; Ludovic Gomez^a ; ^b ; Denis Angoulvant^a ; ^c ; ¹ ; Michel Ovize^a ; ^b ; ^d ; ¹
• 关键词：Coenzyme Q2 ; Mitochondria ; Permeability transition pore ; Hydrogen peroxide ; Complex I
• 刊名：Journal of Molecular and Cellular Cardiology
• 出版年：2012
• 期刊代码：171_00222828
• 类别：bio
• 出版时间：May, 2012
• 卷：52
• 期：5
• 页码：1091-1095
• 文件大小：392 K

摘要

Coenzyme Q₂ (CoQ₂) is known to inhibit mitochondrial permeability transition pore (mPTP) opening in isolated rat liver mitochondria. In this study, we investigated and compared the effects of CoQ₂ on mPTP opening and ROS production in isolated rabbit heart and rat liver mitochondria. Mitochondria were isolated from New Zealand White rabbit hearts and Wistar rat livers. Oxygen consumption, Ca^2 +-induced mPTP opening, ROS production and NADH DUb-reductase activity were measured. Rotenone was used to investigate the effect of CoQ₂ on respiratory complex I activity. CoQ₂ (23 渭M) reduced the respiratory control index by 32%and 57%(p < 0.01) in heart and liver mitochondria respectively, mainly through an increased oxygen consumption in state 4. CoQ₂ induced a 60%(p < 0.05) decrease of calcium retention capacity (CRC) in heart mitochondria and inversely a 46%(p < 0.05) increase in liver mitochondria. In basal condition, CoQ₂ induced a 170%(p < 0.05) increase of H₂O₂ production in heart mitochondria and 21%(ns) decrease of H₂O₂ production in liver mitochondria. Because rotenone, a complex I inhibitor, increases H₂O₂ production in heart but not in liver mitochondria we investigated the CoQ₂ effect in a dose-response assay of complex I inhibition by rotenone in both mitochondria. CoQ₂ antagonized the effect of rotenone on respiratory complex I activity in liver but not in heart mitochondria. CoQ₂ significantly reduced NADH DUb-reductase activity in liver (鈭?#xA0;47%) and heart (鈭?#xA0;37%) mitochondria. In conclusion, our data showed that on the contrary to what was observed in liver mitochondria, CoQ₂ favors mPTP opening and ROS production in heart mitochondria through an opposite effect on respiratory complex I activity.