Alpha-Tocopheryl succinate causes mitochondrial permeabilization by preferential formation of Bak channels

0349091 - BTÚ 2011 RIV NL eng J - Journal Article
Procházka, L. - Dong, L.F. - Vališ, Karel - Freeman, R. - Ralph, S.J. - Turánek, J. - Neužil, Jiří
Alpha-Tocopheryl succinate causes mitochondrial permeabilization by preferential formation of Bak channels.
Apoptosis. Roč. 15, č. 7 (2010), s. 782-794. ISSN 1360-8185. E-ISSN 1573-675X
R&D Projects: GA AV ČR(CZ) KAN200520703; GA AV ČR(CZ) IAA500520702; GA AV ČR(CZ) IAA500520602
Institutional research plan: CEZ:AV0Z50520701
Keywords : Vitamin E succinate * apoptosis * Noxa-Bak
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 4.397, year: 2010

Many mitocans selectively killing cancer cells by destabilizing mitochondria induce apoptosis via generation of reactive oxygen species. In this study with the mitocan alpha-tocopheryl succinate (alpha-TOS) the role of the Bcl-2 family proteins in this mechanism has been determined. Exposure of several different cancer cell lines to alpha-TOS increased expression of the Noxa protein, independently of the cellular p53 status. alpha-TOS caused a profound conformational change in the Bak protein in all cell types, in the Bax protein only in non-small cell lung cancer cells. Immunoprecipitation studies indicated activation of Bak or Bax proteins to form high molecular weight complexes. RNAi knockdown revealed that Noxa and Bak are required for alpha-TOS-induced apoptosis, and the role of Bak was confirmed using Bak- and/or Bax-deficient cells. Then, the events induced by alpha-TOS in cancer cells downstream of ROS production leading to mitochondrial apoptosis involve the Noxa-Bak axis
Permanent Link: http://hdl.handle.net/11104/0189421