title: Bax and heart mitochondria: uncoupling and inhibition of respiration without permeability transition.
abstract: The effects of Bax (full-length, FL, and C-terminal truncated, DeltaC) on respiration rate, membrane potential, MgATPase activity and kinetics of regulation of respiration were studied in isolated rat heart mitochondria and permeabilized cardiomyocytes. The results showed that while both Bax-FL and Bax-DeltaC permeabilized the outer mitochondrial membrane, released cytochrome c and reduced the respiration rate, the latter could be fully restored by exogenous cytochrome c only in the case of Bax-DeltaC, but not in presence of Bax-FL. In addition, Bax-FL but not Bax-DeltaC increased the MgATPase activity, and their effects on the mitochondrial membrane potential were quantitatively different. None of these effects was sensitive to cyclosporin A (CsA). It is concluded that Bax-FL affects both the outer and the inner mitochondrial membranes by: (1) opening large pores in the outer membrane; (2) inhibiting some segments of the respiratory chain in the inner membrane; and (3) uncoupling the inner mitochondrial membrane by increasing proton leak without opening the permeability transition pore (PTP).
authors.affiliation: University of Joseph Fourier, B.P. 35 X, 38041 Cedex 9, Grenoble, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Appaix
authors.forename: Karen
authors.initials: K
authors.lastname: Guerrero
authors.forename: David
authors.initials: D
authors.lastname: Rampal
authors.forename: Mohamed
authors.initials: M
authors.lastname: Izikki
authors.forename: Tuuli
authors.initials: T
authors.lastname: Kaambre
authors.forename: Peeter
authors.initials: P
authors.lastname: Sikk
authors.forename: Dieter
authors.initials: D
authors.lastname: Brdiczka
authors.forename: Catherine
authors.initials: C
authors.lastname: Riva-Lavieille
authors.forename: Jose
authors.initials: J
authors.lastname: Olivares
authors.forename: Michel
authors.initials: M
authors.lastname: Longuet
authors.forename: Bruno
authors.initials: B
authors.lastname: Antonsson
authors.forename: Valdur A
authors.initials: VA
authors.lastname: Saks
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002458:Cell Fractionation; D019069:Cell Respiration / Q000502:physiology*; D003574:Cytochrome c Group / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology*; D008929:Mitochondria, Heart / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D017208:Rats, Wistar; D014475:Uncoupling Agents / Q000378:metabolism; D051028:bcl-2-Associated X Protein
chemical_list: C494828:Bax protein, rat; D003574:Cytochrome c Group; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014475:Uncoupling Agents; D051028:bcl-2-Associated X Protein; D000244:Adenosine Diphosphate; D017301:Ca(2+) Mg(2+)-ATPase; D010100:Oxygen