Appaix Florence, Guerrero Karen, Rampal David, Izikki Mohamed, Kaambre Tuuli, Sikk Peeter, Brdiczka Dieter, Riva-Lavieille Catherine, Olivares Jose, Longuet Michel, Antonsson Bruno, Saks Valdur A
University of Joseph Fourier, B.P. 35 X, 38041 Cedex 9, Grenoble, France.
Biochim Biophys Acta. 2002 Dec 2;1556(2-3):155-67. doi: 10.1016/s0005-2728(02)00358-4.
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).
在分离的大鼠心脏线粒体和透化心肌细胞中，研究了Bax（全长，FL，和C端截短型，DeltaC）对呼吸速率、膜电位、MgATP酶活性以及呼吸调节动力学的影响。结果表明，虽然Bax-FL和Bax-DeltaC均能使线粒体外膜通透化，释放细胞色素c并降低呼吸速率，但仅在Bax-DeltaC的情况下，外源性细胞色素c可使其呼吸速率完全恢复，而在Bax-FL存在时则不能。此外，Bax-FL而非Bax-DeltaC增加了MgATP酶活性，并且它们对线粒体膜电位的影响在数量上有所不同。这些效应均对环孢素A（CsA）不敏感。结论是，Bax-FL通过以下方式影响线粒体外膜和内膜：（1）在外膜上形成大孔；（2）抑制内膜中呼吸链的某些片段；（3）通过增加质子泄漏使线粒体内膜解偶联，而不打开通透性转换孔（PTP）。
