Mitochondrial Binding of Hexokinase II Inhibits Bax-induced CytochromecRelease and Apoptosis

作者: John G. Pastorino , Nataly Shulga , Jan B. Hoek

DOI: 10.1074/JBC.M109950200

关键词:

摘要: Proapoptotic proteins such as Bax, undergo translocation to the mitochondria during apoptosis, where they mediate release of intermembrane space including cytochromec. Bax binds voltage-dependent anion channel (VDAC). VDAC is a β-barrel protein located in outer mitochondrial membrane. In planar lipid bilayers, and form through which cytochrome c can pass. Hexokinase II (HXK II) also VDAC. HXK catalyzes first step glycolysis highly expressed transformed cells, over 70% it bound mitochondria. The present study demonstrates that interferes with ability bind c. Detachment from mitochondria-enriched fraction isolated HeLa cells promoted binding recombinant Bax-Δ19 subsequent cytochromec release. Similarly, addition hepatocytes, do not express endogenously, prevented promote Similar results were found intact detachment or its overexpression potentiated inhibited, respectively, Bax-induced dysfunction cell death.

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