Respiration and substrate transport rates as well as reactive oxygen species production distinguish mitochondria from brain and liver.

Autor: Gusdon AM; 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., Fernandez-Bueno GA; Department of Pathology, Immunology, and Laboratory Medicine, The University of Florida College of Medicine, Gainesville, FL, 32610, USA. gfernandezbueno@ufl.edu., Wohlgemuth S; Department of Animal Sciences, Institute of Food and Agricultural Sciences, The University of Florida, Gainesville, FL, 32610, USA. steffiw@ufl.edu., Fernandez J; Department of Pathology, Immunology, and Laboratory Medicine, The University of Florida College of Medicine, Gainesville, FL, 32610, USA. jenelle@ufl.edu., Chen J; Department of Pathology, Immunology, and Laboratory Medicine, The University of Florida College of Medicine, Gainesville, FL, 32610, USA. jic24@ufl.edu., Mathews CE; 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.
Jazyk: angličtina
Zdroj: BMC biochemistry [BMC Biochem] 2015 Sep 10; Vol. 16, pp. 22. Date of Electronic Publication: 2015 Sep 10.
DOI: 10.1186/s12858-015-0051-8
Abstrakt: 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.
Databáze: MEDLINE
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