title: Respiration and substrate transport rates as well as reactive oxygen species production distinguish mitochondria from brain and liver.
abstract: BACKGROUND
  Aberrant mitochondrial function, including excessive reactive oxygen species (ROS) production, has been implicated in the pathogenesis of human diseases. The use of mitochondrial inhibitors to ascertain the sites in the electron transport chain (ETC) resulting in altered ROS production can be an important tool. However, the response of mouse mitochondria to ETC inhibitors has not been thoroughly assessed. Here we set out to characterize the differences in phenotypic response to ETC inhibitors between the more energetically demanding brain mitochondria and less energetically demanding liver mitochondria in commonly utilized C57BL/6J mice.
  
  
  RESULTS
  We show that in contrast to brain mitochondria, inhibiting distally within complex I or within complex III does not increase liver mitochondrial ROS production supported by complex I substrates, and liver mitochondrial ROS production supported by complex II substrates occurred primarily independent of membrane potential. Complex I, II, and III enzymatic activities and membrane potential were equivalent between liver and brain and responded to ETC. inhibitors similarly. Brain mitochondria exhibited an approximately two-fold increase in complex I and II supported respiration compared with liver mitochondria while exhibiting similar responses to inhibitors. Elevated NADH transport and heightened complex II-III coupled activity accounted for increased complex I and II supported respiration, respectively in brain mitochondria.
  
  
  CONCLUSIONS
  We conclude that important mechanistic differences exist between mouse liver and brain mitochondria and that mouse mitochondria exhibit phenotypic differences compared with mitochondria from other species.
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, The University of Florida College of Medicine, Gainesville, FL, 32610, USA. amg9048@nyp.org.|Department of Neurology, Weill Cornell Medical Center/NewYork-Presbyterian Hospital, New York, NY, 10065, USA. amg9048@nyp.org.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Gusdon
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, The University of Florida College of Medicine, Gainesville, FL, 32610, USA. gfernandezbueno@ufl.edu.
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Fernandez-Bueno
authors.affiliation: Department of Animal Sciences, Institute of Food and Agricultural Sciences, The University of Florida, Gainesville, FL, 32610, USA. steffiw@ufl.edu.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Wohlgemuth
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, The University of Florida College of Medicine, Gainesville, FL, 32610, USA. jenelle@ufl.edu.
authors.forename: Jenelle
authors.initials: J
authors.lastname: Fernandez
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, The University of Florida College of Medicine, Gainesville, FL, 32610, USA. jic24@ufl.edu.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, The University of Florida College of Medicine, Gainesville, FL, 32610, USA. clayton.mathews@pathology.ufl.edu.|, Present address: 1275 Center Dr, Room J597, P.O. Box 100275, Gainesville, FL, 32610-0275, USA. clayton.mathews@pathology.ufl.edu.
authors.forename: Clayton E
authors.initials: CE
authors.lastname: Mathews
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000166:cytology*; D019069:Cell Respiration / Q000187:drug effects; D029382:Dicarboxylic Acid Transporters / Q000235:genetics; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000166:cytology*; D008293:Malates / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D009928:Organ Specificity; D017382:Reactive Oxygen Species / Q000378:metabolism*; D019802:Succinic Acid / Q000378:metabolism
chemical_list: D029382:Dicarboxylic Acid Transporters; D045222:Electron Transport Chain Complex Proteins; D004791:Enzyme Inhibitors; D008293:Malates; D017382:Reactive Oxygen Species; C504725:Slc25a10 protein, mouse; D009243:NAD; D001224:Aspartic Acid; D018698:Glutamic Acid; C030298:malic acid; D019802:Succinic Acid