title: Opposite and tissue-specific effects of coenzyme Q2 on mPTP opening and ROS production between heart and liver mitochondria: role of complex I.
abstract: Coenzyme Q(2) (CoQ(2)) 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 CoQ(2) 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 CoQ(2) on respiratory complex I activity. CoQ(2) (23 μM) 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. CoQ(2) 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, CoQ(2) induced a 170% (p<0.05) increase of H(2)O(2) production in heart mitochondria and 21% (ns) decrease of H(2)O(2) production in liver mitochondria. Because rotenone, a complex I inhibitor, increases H(2)O(2) production in heart but not in liver mitochondria we investigated the CoQ(2) effect in a dose-response assay of complex I inhibition by rotenone in both mitochondria. CoQ(2) antagonized the effect of rotenone on respiratory complex I activity in liver but not in heart mitochondria. CoQ(2) significantly reduced NADH DUb-reductase activity in liver (-47%) and heart (-37%) mitochondria. In conclusion, our data showed that on the contrary to what was observed in liver mitochondria, CoQ(2) favors mPTP opening and ROS production in heart mitochondria through an opposite effect on respiratory complex I activity.
authors.affiliation: INSERM UMR 1060, CarMeN, F-69373, Lyon, France. abdallah.gharib@univ-lyon1.fr
authors.forename: Abdallah
authors.initials: A
authors.lastname: Gharib
authors.forename: Damien
authors.initials: D
authors.lastname: De Paulis
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Lionel
authors.initials: L
authors.lastname: Augeul
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Couture-Lepetit
authors.forename: Ludovic
authors.initials: L
authors.lastname: Gomez
authors.forename: Denis
authors.initials: D
authors.lastname: Angoulvant
authors.forename: Michel
authors.initials: M
authors.lastname: Ovize
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D042967:Electron Transport Complex I / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000494:pharmacology; D019802:Succinic Acid / Q000378:metabolism; D014451:Ubiquinone / Q000502:physiology*; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species; D014475:Uncoupling Agents; D012402:Rotenone; D014451:Ubiquinone; D019802:Succinic Acid; D006861:Hydrogen Peroxide; D042967:Electron Transport Complex I; C025204:Ubiquinone Q2; D002118:Calcium