title: Cardiolipin fatty acid remodeling regulates mitochondrial function by modifying the electron entry point in the respiratory chain.
abstract: Modifications of cardiolipin (CL) levels or compositions are associated with changes in mitochondrial function in a wide range of pathologies. We have made the discovery that acetaminophen remodels CL fatty acids composition from tetralinoleoyl to linoleoyltrioleoyl-CL, a remodeling that is associated with decreased mitochondrial respiration. Our data show that CL remodeling causes a shift in electron entry from complex II to the β-oxidation electron transfer flavoprotein quinone oxidoreductase (ETF/QOR) pathway. These data demonstrate that electron entry in the respiratory chain is regulated by CL fatty acid composition and provide proof-of-concept that pharmacological intervention can be used to modify CL composition.
authors.affiliation: Department of Pharmacology, Vanderbilt University Medical Center, 536 Robinson Research Building, Nashville, TN 37232-6602, United States.
authors.forename: Aurelia
authors.initials: A
authors.lastname: Vergeade
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University Medical Center, 536 Robinson Research Building, Nashville, TN 37232-6602, United States.
authors.forename: Clinton C
authors.initials: CC
authors.lastname: Bertram
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, 536 Robinson Research Building, Nashville, TN 37232-6602, United States.
authors.forename: Alfiya T
authors.initials: AT
authors.lastname: Bikineyeva
authors.affiliation: Department of Pharmacology, Vanderbilt University Medical Center, 536 Robinson Research Building, Nashville, TN 37232-6602, United States.
authors.forename: William E
authors.initials: WE
authors.lastname: Zackert
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University Medical Center, 536 Robinson Research Building, Nashville, TN 37232-6602, United States; Department of Medicine, Vanderbilt University Medical Center, 536 Robinson Research Building, Nashville, TN 37232-6602, United States.
authors.forename: Sandra S
authors.initials: SS
authors.lastname: Zinkel
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, 536 Robinson Research Building, Nashville, TN 37232-6602, United States.
authors.forename: James M
authors.initials: JM
authors.lastname: May
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, 536 Robinson Research Building, Nashville, TN 37232-6602, United States.
authors.forename: Sergey I
authors.initials: SI
authors.lastname: Dikalov
authors.affiliation: Department of Pharmacology, Vanderbilt University Medical Center, 536 Robinson Research Building, Nashville, TN 37232-6602, United States; Department of Medicine, Vanderbilt University Medical Center, 536 Robinson Research Building, Nashville, TN 37232-6602, United States.
authors.forename: L Jackson
authors.initials: LJ
authors.lastname: Roberts
authors.affiliation: Department of Pharmacology, Vanderbilt University Medical Center, 536 Robinson Research Building, Nashville, TN 37232-6602, United States. Electronic address: olivier.boutaud@vanderbilt.edu.
authors.forename: Olivier
authors.initials: O
authors.lastname: Boutaud
mesh_terms: D000082:Acetaminophen / Q000378:metabolism*; D058633:Antipyretics / Q000378:metabolism*; D002308:Cardiolipins / Q000378:metabolism*; D019069:Cell Respiration / Q000187:drug effects; D002478:Cells, Cultured; D004579:Electron Transport; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000737:chemistry / Q000187:drug effects*; D023461:Myeloid Progenitor Cells / Q000187:drug effects / Q000378:metabolism; D011809:Quinones / Q000032:analysis
chemical_list: D058633:Antipyretics; D002308:Cardiolipins; D005227:Fatty Acids; D011809:Quinones; D000082:Acetaminophen
keywords: Acetaminophen; Cardiolipin; Electron entry point; Electron transport chain; Mitochondria