Announcement iconContinuing Accepting Applications for Admission !!
for the Spring Semester of the Academic Year 2019/2020

The voltage-dependent anion channel modulates apoptotic cell death

Authors: 
Zaid H.
Abu-Hamad S.
Israelson A.
Nathan I.
Shoshan-Barmatz V.
Journal Name: 
Cell death and differentiation
Volume: 
12
Issue: 
7
Pages From: 
751
To: 
760
Date: 
Friday, July 1, 2005
Keywords: 
apoptosis, hexokinase, mitochondria, ruthenium red, VDAC
Abstract: 
The role of the voltage-dependent anion channel (VDAC) in cell death was investigated using the expression of native and mutated murine VDAC1 in U-937 cells and VDAC inhibitors. Glutamate 72 in VDAC1, shown previously to bind dicyclohexylcarbodiimide (DCCD), which inhibits hexokinase isoform I (HK-I) binding to mitochondria, was mutated to glutamine. Binding of HK-I to mitochondria expressing E72Q-mVDAC1, as compared to native VDAC1, was decreased by approx70% and rendered insensitive to DCCD. HK-I and ruthenium red (RuR) reduced the VDAC1 conductance but not that of E72Q-mVDAC1. Overexpression of native or E72Q-mVDAC1 in U-937 cells induced apoptotic cell death (80%). RuR or overexpression of HK-I prevented this apoptosis in cells expressing native but not E72Q-mVDAC1. Thus, a single amino-acid mutation in VDAC prevented HK-I- or RuR-mediated protection against apoptosis, suggesting the direct VDAC regulation of the mitochondria-mediated apoptotic pathway and that the protective effects of RuR and HK-I rely on their binding to VDAC.