The porin VDAC2 is the mitochondrial platform for Bax retrotranslocation

被引：68

作者：

Lauterwasser, Joachim ^{[1
,2
]}

Todt, Franziska ^{[1
,3
]}

Zerbes, Ralf M. ^{[1
,2
]}

Thanh Ngoc Nguyen ^{[4
]}

Craigen, William ^{[5
]}

Lazarou, Michael ^{[4
]}

van der Laan, Martin ^{[1
,6
,7
]}

Edlich, Frank ^{[1
,7
]}

机构：

[1] Univ Freiburg, Fac Med, ZBMZ, Inst Biochem & Mol Biol, D-79104 Freiburg, Germany

[2] Univ Freiburg, Fac Biol, D-79104 Freiburg, Germany

[3] SGBM, Spemann Grad Sch Biol & Med, D-79104 Freiburg, Germany

[4] Monash Univ, Dept Biochem & Mol Biol, Melbourne, Vic, Australia

[5] Texas Childrens Hosp, Genet, Dept Pediat Med, Houston, TX 77030 USA

[6] Univ Saarland, Med Biochem & Mol Biol, D-66421 Homburg, Germany

[7] Univ Freiburg, Ctr Biol Signaling Studies, BIOSS, D-79104 Freiburg, Germany

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

关键词：

DEPENDENT ANION CHANNELS; PERMEABILITY TRANSITION PORE; CYTOCHROME-C RELEASE; CELL-DEATH; PROTEIN; ACTIVATION; BINDING; CYTOSOL; OLIGOMERIZATION; MECHANISMS;

D O I：

10.1038/srep32994

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

The pro-apoptotic Bcl-2 protein Bax can permeabilize the outer mitochondrial membrane and therefore commit human cells to apoptosis. Bax is regulated by constant translocation to the mitochondria and retrotranslocation back into the cytosol. Bax retrotranslocation depends on pro-survival Bcl-2 proteins and stabilizes inactive Bax. Here we show that Bax retrotranslocation shuttles membrane-associated and membrane-integral Bax from isolated mitochondria. We further discover the mitochondrial porin voltage-dependent anion channel 2 (VDAC2) as essential component and platform for Bax retrotranslocation. VDAC2 ensures mitochondria-specific membrane association of Bax and in the absence of VDAC2 Bax localizes towards other cell compartments. Bax retrotranslocation is also regulated by nucleotides and calcium ions, suggesting a potential role of the transport of these ions through VDAC2 in Bax retrotranslocation. Together, our results reveal the unanticipated bifunctional role of VDAC2 to target Bax specifically to the mitochondria and ensure Bax inhibition by retrotranslocation into the cytosol.

引用

页数：11

共 46 条

[1]

Charged Residues Distribution Modulates Selectivity of the Open State of Human Isoforms of the Voltage Dependent Anion-Selective Channel [J].