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Essential role of voltage-dependent anion channel in various forms of apoptosis in mammalian cells.

Shimizu S, Matsuoka Y, Shinohara Y, Yoneda Y, Tsujimoto Y - J. Cell Biol. (2001)

Bottom Line: Through direct interaction with the voltage-dependent anion channel (VDAC), proapoptotic members of the Bcl-2 family such as Bax and Bak induce apoptogenic cytochrome c release in isolated mitochondria, whereas BH3-only proteins such as Bid and Bik do not directly target the VDAC to induce cytochrome c release.When microinjected into cells, these anti-VDAC antibodies, but not control antibodies, also prevented Bax-induced cytochrome c release and apoptosis, whereas the antibodies did not prevent Bid-induced apoptosis, indicating that the VDAC is essential for Bax-induced, but not Bid-induced, apoptogenic mitochondrial changes and apoptotic cell death.Taken together, our data provide evidence that the VDAC plays an essential role in apoptogenic cytochrome c release and apoptosis in mammalian cells.

View Article: PubMed Central - PubMed

Affiliation: Osaka University Graduate School of Medicine, Biomedical Research Center, Department of Medical Genetics, Osaka 565-0871, Japan.

ABSTRACT
Through direct interaction with the voltage-dependent anion channel (VDAC), proapoptotic members of the Bcl-2 family such as Bax and Bak induce apoptogenic cytochrome c release in isolated mitochondria, whereas BH3-only proteins such as Bid and Bik do not directly target the VDAC to induce cytochrome c release. To investigate the biological significance of the VDAC for apoptosis in mammalian cells, we produced two kinds of anti-VDAC antibodies that inhibited VDAC activity. In isolated mitochondria, these antibodies prevented Bax-induced cytochrome c release and loss of the mitochondrial membrane potential (Deltapsi), but not Bid-induced cytochrome c release. When microinjected into cells, these anti-VDAC antibodies, but not control antibodies, also prevented Bax-induced cytochrome c release and apoptosis, whereas the antibodies did not prevent Bid-induced apoptosis, indicating that the VDAC is essential for Bax-induced, but not Bid-induced, apoptogenic mitochondrial changes and apoptotic cell death. In addition, microinjection of these anti-VDAC antibodies significantly inhibited etoposide-, paclitaxel-, and staurosporine-induced apoptosis. Furthermore, we used these antibodies to show that Bax- and Bak-induced lysis of red blood cells was also mediated by the VDAC on plasma membrane. Taken together, our data provide evidence that the VDAC plays an essential role in apoptogenic cytochrome c release and apoptosis in mammalian cells.

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Inhibition of rBax-induced release of hemoglobin from RBCs by addition of anti-VDAC antibodies. (A–D) Detection of VDAC on the RBC plasma membrane. (A) RBCs, at 0.25% (vol/vol), were incubated with 0.4 μg/μl of Ab#25 or NRI for 30 min. After washing twice, anti–rabbit IgG-Alexa488 was added to the cells for 30 min and then the RBCs were analyzed using a flow cytometer. (B) Whole lysates of RBCs (40 μg) and HeLa cells (3 μg) were subjected to Western blot analysis using anti-VDAC antibody (31HL and Ab#25) and anticytochrome c antibody. (C and D) RBCs (40 μl), at 15% (vol/vol), were incubated with (+) or without (−) 1% trypsin for 1 h at 25°C, followed by incubation with 3% trypsin inhibitor for 30 min (C). RBCs were also incubated with an equivalent volume of distilled water (D.W.+) to produce ghost RBCs or 0.9% NaCl (D.W.−) for 30 min (D). After brief centrifugation, half of trypsin-treated RBCs and ghost RBC lysates were subjected to Western blot analysis using anti-VDAC antibody (31HL) and anti-GPDH antibody. (E) Interaction of rBax with VDAC on RBCs. RBCs (100 μl), at 15% (vol/vol), were incubated with 50 μg of rBax for 15 min at 25°C. Then, RBCs were lysed and immunoprecipitated with anti-Bax antibody (α-Bax), anti-VDAC antibody (31HL) (α-VDAC), NRI, or normal mouse IgG. Immune complexes were analyzed by Western blotting. “Total” represents 1/10 the amount of lysates used for the experiment. (F–H) Inhibition of Bax- and Bak-induced release of hemoglobin from RBCs by Ab#20 and Ab#25. All data are indicated as mean ± SD for three independent experiments. (F) RBCs, at 2.5% (vol/vol), were preincubated for 5 min with Ab#25 (filled circles), or NRI (open circles) at 0.8 μg/μl, or were preincubated without antibodies (open triangles), and then were incubated with rBax (1 μg/μl). RBCs were also incubated with an equivalent amount of irrelevant protein (open squares) for the indicated times. Then, the RBCs were spun, and free hemoglobin was detected at OD543 using a spectrophotometer. The total hemoglobin content was estimated after hypotonic lysis of RBCs (filled triangle). (G) A similar procedure as described in F was performed with the indicated concentrations of Ab#20 (filled squares), Ab#25 (filled circles), or NRI (open circles) for 5 min, followed by incubation with rBax (1 μg/μl) for 1 h. The total hemoglobin content was estimated after hypotonic lysis of RBCs (filled triangle). (H) A similar procedure as described in F was performed with Ab#25 (black bars), or NRI (white bars) for 5 min at 0.8 μg/μl, followed by incubation with rBak (1 μg/μl) or an equivalent amount of irrelevant protein for 1 h. Free hemoglobin was assessed. (I) Flow cytometric analysis of RBCs stained with Ab#25. RBCs, at 2.5% (vol/vol), were incubated with Ab#25 (open circles) or NRI (filled circle) at the indicated concentrations, and then stained with anti–rabbit IgG-Alexa488. Fluorescence was measured by flow cytometry as described in Materials and Methods. Data are indicated as mean ± SD for three independent experiments. (J) Inhibition of Bak-induced release of hemoglobin from RBCs by Bcl-xL BH4 peptide. A similar procedure as described in H was performed with the BH4 peptide (open circles) or BH4 mutant ΔFL peptide (filled circles) for 5 min at the indicated concentrations, followed by incubation with rBak (1 μg/μl) for 1 h. Data are indicated as mean ± SD for three independent experiments. (K) Lack of effect of Ab#20 and Ab#25 on hemolysin-induced release of hemoglobin from RBCs. RBCs, at 2.5% (vol/vol), were preincubated with Ab#20, Ab#25, or NRI at 0.8 μg/μl for 5 min, and then were incubated with Kanagawa (K) hemolysin at the indicated concentrations for 1 h. Free hemoglobin was detected at OD543 using a spectrophotometer. The total hemoglobin content was estimated after hypotonic lysis (filled triangle). Data are indicated as mean ± SD for three independent experiments.
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Figure 7: Inhibition of rBax-induced release of hemoglobin from RBCs by addition of anti-VDAC antibodies. (A–D) Detection of VDAC on the RBC plasma membrane. (A) RBCs, at 0.25% (vol/vol), were incubated with 0.4 μg/μl of Ab#25 or NRI for 30 min. After washing twice, anti–rabbit IgG-Alexa488 was added to the cells for 30 min and then the RBCs were analyzed using a flow cytometer. (B) Whole lysates of RBCs (40 μg) and HeLa cells (3 μg) were subjected to Western blot analysis using anti-VDAC antibody (31HL and Ab#25) and anticytochrome c antibody. (C and D) RBCs (40 μl), at 15% (vol/vol), were incubated with (+) or without (−) 1% trypsin for 1 h at 25°C, followed by incubation with 3% trypsin inhibitor for 30 min (C). RBCs were also incubated with an equivalent volume of distilled water (D.W.+) to produce ghost RBCs or 0.9% NaCl (D.W.−) for 30 min (D). After brief centrifugation, half of trypsin-treated RBCs and ghost RBC lysates were subjected to Western blot analysis using anti-VDAC antibody (31HL) and anti-GPDH antibody. (E) Interaction of rBax with VDAC on RBCs. RBCs (100 μl), at 15% (vol/vol), were incubated with 50 μg of rBax for 15 min at 25°C. Then, RBCs were lysed and immunoprecipitated with anti-Bax antibody (α-Bax), anti-VDAC antibody (31HL) (α-VDAC), NRI, or normal mouse IgG. Immune complexes were analyzed by Western blotting. “Total” represents 1/10 the amount of lysates used for the experiment. (F–H) Inhibition of Bax- and Bak-induced release of hemoglobin from RBCs by Ab#20 and Ab#25. All data are indicated as mean ± SD for three independent experiments. (F) RBCs, at 2.5% (vol/vol), were preincubated for 5 min with Ab#25 (filled circles), or NRI (open circles) at 0.8 μg/μl, or were preincubated without antibodies (open triangles), and then were incubated with rBax (1 μg/μl). RBCs were also incubated with an equivalent amount of irrelevant protein (open squares) for the indicated times. Then, the RBCs were spun, and free hemoglobin was detected at OD543 using a spectrophotometer. The total hemoglobin content was estimated after hypotonic lysis of RBCs (filled triangle). (G) A similar procedure as described in F was performed with the indicated concentrations of Ab#20 (filled squares), Ab#25 (filled circles), or NRI (open circles) for 5 min, followed by incubation with rBax (1 μg/μl) for 1 h. The total hemoglobin content was estimated after hypotonic lysis of RBCs (filled triangle). (H) A similar procedure as described in F was performed with Ab#25 (black bars), or NRI (white bars) for 5 min at 0.8 μg/μl, followed by incubation with rBak (1 μg/μl) or an equivalent amount of irrelevant protein for 1 h. Free hemoglobin was assessed. (I) Flow cytometric analysis of RBCs stained with Ab#25. RBCs, at 2.5% (vol/vol), were incubated with Ab#25 (open circles) or NRI (filled circle) at the indicated concentrations, and then stained with anti–rabbit IgG-Alexa488. Fluorescence was measured by flow cytometry as described in Materials and Methods. Data are indicated as mean ± SD for three independent experiments. (J) Inhibition of Bak-induced release of hemoglobin from RBCs by Bcl-xL BH4 peptide. A similar procedure as described in H was performed with the BH4 peptide (open circles) or BH4 mutant ΔFL peptide (filled circles) for 5 min at the indicated concentrations, followed by incubation with rBak (1 μg/μl) for 1 h. Data are indicated as mean ± SD for three independent experiments. (K) Lack of effect of Ab#20 and Ab#25 on hemolysin-induced release of hemoglobin from RBCs. RBCs, at 2.5% (vol/vol), were preincubated with Ab#20, Ab#25, or NRI at 0.8 μg/μl for 5 min, and then were incubated with Kanagawa (K) hemolysin at the indicated concentrations for 1 h. Free hemoglobin was detected at OD543 using a spectrophotometer. The total hemoglobin content was estimated after hypotonic lysis (filled triangle). Data are indicated as mean ± SD for three independent experiments.

Mentions: It has previously been reported that addition of rBax induces lysis of RBCs, and this hemolysis has been considered to be due to formation of the Bax channel on the RBC membrane (Antonsson et al. 1997). Since VDAC is also known to be located on the plasma membrane (Cole et al. 1992; Buettner et al. 2000), the possibility was raised that Bax-mediated RBC lysis was also mediated by the VDAC. The presence of the VDAC on RBC plasma membrane was confirmed by flow cytometry (Fig. 7 A), which also showed that it was oriented with the epitope for Ab#25 facing outside, consistent with previous observations (Cole et al. 1992). Since RBCs do not possess mitochondria, which was confirmed by the absence of cytochrome c (Fig. 7 B), and since they have no ER and Golgi apparatus, the VDAC shown by Western blotting (Fig. 7 B) probably largely represented VDAC on the plasma membrane. The VDAC on RBCs was ∼1 kD smaller than that in HeLa cells (Fig. 7 B), but reacted with all the anti-VDAC antibodies (31HL, Ab#25 [Fig. 7 B], Ab#20, and an antibody whose epitope was amino acids 177–192 [data not shown]), and, therefore, the VDAC on RBCs probably represents a splicing variant or is subjected to RBC-specific modifications. Several erythrocyte-specific alterations of proteins have been reported, for example, hexokinase and pyruvate kinases (Lacrinique et al. 1992; Murakami and Piomelli 1997). The possibility was not excluded that the VDAC on RBCs represents a protein highly related to VDAC or another member of the VDAC family. The presence of the VDAC on RBC plasma membrane was also confirmed by tryptic digestion of VDAC but not glyceraldehyde 3-phosphate dehydrogenase (GPDH), a cytosolic glycolytic enzyme (Fig. 7 C), and by the presence of VDAC in ghost RBCs (Fig. 7 D). Like mitochondrial VDAC, VDAC in RBCs bound to rBax (Fig. 7 E).


Essential role of voltage-dependent anion channel in various forms of apoptosis in mammalian cells.

Shimizu S, Matsuoka Y, Shinohara Y, Yoneda Y, Tsujimoto Y - J. Cell Biol. (2001)

Inhibition of rBax-induced release of hemoglobin from RBCs by addition of anti-VDAC antibodies. (A–D) Detection of VDAC on the RBC plasma membrane. (A) RBCs, at 0.25% (vol/vol), were incubated with 0.4 μg/μl of Ab#25 or NRI for 30 min. After washing twice, anti–rabbit IgG-Alexa488 was added to the cells for 30 min and then the RBCs were analyzed using a flow cytometer. (B) Whole lysates of RBCs (40 μg) and HeLa cells (3 μg) were subjected to Western blot analysis using anti-VDAC antibody (31HL and Ab#25) and anticytochrome c antibody. (C and D) RBCs (40 μl), at 15% (vol/vol), were incubated with (+) or without (−) 1% trypsin for 1 h at 25°C, followed by incubation with 3% trypsin inhibitor for 30 min (C). RBCs were also incubated with an equivalent volume of distilled water (D.W.+) to produce ghost RBCs or 0.9% NaCl (D.W.−) for 30 min (D). After brief centrifugation, half of trypsin-treated RBCs and ghost RBC lysates were subjected to Western blot analysis using anti-VDAC antibody (31HL) and anti-GPDH antibody. (E) Interaction of rBax with VDAC on RBCs. RBCs (100 μl), at 15% (vol/vol), were incubated with 50 μg of rBax for 15 min at 25°C. Then, RBCs were lysed and immunoprecipitated with anti-Bax antibody (α-Bax), anti-VDAC antibody (31HL) (α-VDAC), NRI, or normal mouse IgG. Immune complexes were analyzed by Western blotting. “Total” represents 1/10 the amount of lysates used for the experiment. (F–H) Inhibition of Bax- and Bak-induced release of hemoglobin from RBCs by Ab#20 and Ab#25. All data are indicated as mean ± SD for three independent experiments. (F) RBCs, at 2.5% (vol/vol), were preincubated for 5 min with Ab#25 (filled circles), or NRI (open circles) at 0.8 μg/μl, or were preincubated without antibodies (open triangles), and then were incubated with rBax (1 μg/μl). RBCs were also incubated with an equivalent amount of irrelevant protein (open squares) for the indicated times. Then, the RBCs were spun, and free hemoglobin was detected at OD543 using a spectrophotometer. The total hemoglobin content was estimated after hypotonic lysis of RBCs (filled triangle). (G) A similar procedure as described in F was performed with the indicated concentrations of Ab#20 (filled squares), Ab#25 (filled circles), or NRI (open circles) for 5 min, followed by incubation with rBax (1 μg/μl) for 1 h. The total hemoglobin content was estimated after hypotonic lysis of RBCs (filled triangle). (H) A similar procedure as described in F was performed with Ab#25 (black bars), or NRI (white bars) for 5 min at 0.8 μg/μl, followed by incubation with rBak (1 μg/μl) or an equivalent amount of irrelevant protein for 1 h. Free hemoglobin was assessed. (I) Flow cytometric analysis of RBCs stained with Ab#25. RBCs, at 2.5% (vol/vol), were incubated with Ab#25 (open circles) or NRI (filled circle) at the indicated concentrations, and then stained with anti–rabbit IgG-Alexa488. Fluorescence was measured by flow cytometry as described in Materials and Methods. Data are indicated as mean ± SD for three independent experiments. (J) Inhibition of Bak-induced release of hemoglobin from RBCs by Bcl-xL BH4 peptide. A similar procedure as described in H was performed with the BH4 peptide (open circles) or BH4 mutant ΔFL peptide (filled circles) for 5 min at the indicated concentrations, followed by incubation with rBak (1 μg/μl) for 1 h. Data are indicated as mean ± SD for three independent experiments. (K) Lack of effect of Ab#20 and Ab#25 on hemolysin-induced release of hemoglobin from RBCs. RBCs, at 2.5% (vol/vol), were preincubated with Ab#20, Ab#25, or NRI at 0.8 μg/μl for 5 min, and then were incubated with Kanagawa (K) hemolysin at the indicated concentrations for 1 h. Free hemoglobin was detected at OD543 using a spectrophotometer. The total hemoglobin content was estimated after hypotonic lysis (filled triangle). Data are indicated as mean ± SD for three independent experiments.
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Figure 7: Inhibition of rBax-induced release of hemoglobin from RBCs by addition of anti-VDAC antibodies. (A–D) Detection of VDAC on the RBC plasma membrane. (A) RBCs, at 0.25% (vol/vol), were incubated with 0.4 μg/μl of Ab#25 or NRI for 30 min. After washing twice, anti–rabbit IgG-Alexa488 was added to the cells for 30 min and then the RBCs were analyzed using a flow cytometer. (B) Whole lysates of RBCs (40 μg) and HeLa cells (3 μg) were subjected to Western blot analysis using anti-VDAC antibody (31HL and Ab#25) and anticytochrome c antibody. (C and D) RBCs (40 μl), at 15% (vol/vol), were incubated with (+) or without (−) 1% trypsin for 1 h at 25°C, followed by incubation with 3% trypsin inhibitor for 30 min (C). RBCs were also incubated with an equivalent volume of distilled water (D.W.+) to produce ghost RBCs or 0.9% NaCl (D.W.−) for 30 min (D). After brief centrifugation, half of trypsin-treated RBCs and ghost RBC lysates were subjected to Western blot analysis using anti-VDAC antibody (31HL) and anti-GPDH antibody. (E) Interaction of rBax with VDAC on RBCs. RBCs (100 μl), at 15% (vol/vol), were incubated with 50 μg of rBax for 15 min at 25°C. Then, RBCs were lysed and immunoprecipitated with anti-Bax antibody (α-Bax), anti-VDAC antibody (31HL) (α-VDAC), NRI, or normal mouse IgG. Immune complexes were analyzed by Western blotting. “Total” represents 1/10 the amount of lysates used for the experiment. (F–H) Inhibition of Bax- and Bak-induced release of hemoglobin from RBCs by Ab#20 and Ab#25. All data are indicated as mean ± SD for three independent experiments. (F) RBCs, at 2.5% (vol/vol), were preincubated for 5 min with Ab#25 (filled circles), or NRI (open circles) at 0.8 μg/μl, or were preincubated without antibodies (open triangles), and then were incubated with rBax (1 μg/μl). RBCs were also incubated with an equivalent amount of irrelevant protein (open squares) for the indicated times. Then, the RBCs were spun, and free hemoglobin was detected at OD543 using a spectrophotometer. The total hemoglobin content was estimated after hypotonic lysis of RBCs (filled triangle). (G) A similar procedure as described in F was performed with the indicated concentrations of Ab#20 (filled squares), Ab#25 (filled circles), or NRI (open circles) for 5 min, followed by incubation with rBax (1 μg/μl) for 1 h. The total hemoglobin content was estimated after hypotonic lysis of RBCs (filled triangle). (H) A similar procedure as described in F was performed with Ab#25 (black bars), or NRI (white bars) for 5 min at 0.8 μg/μl, followed by incubation with rBak (1 μg/μl) or an equivalent amount of irrelevant protein for 1 h. Free hemoglobin was assessed. (I) Flow cytometric analysis of RBCs stained with Ab#25. RBCs, at 2.5% (vol/vol), were incubated with Ab#25 (open circles) or NRI (filled circle) at the indicated concentrations, and then stained with anti–rabbit IgG-Alexa488. Fluorescence was measured by flow cytometry as described in Materials and Methods. Data are indicated as mean ± SD for three independent experiments. (J) Inhibition of Bak-induced release of hemoglobin from RBCs by Bcl-xL BH4 peptide. A similar procedure as described in H was performed with the BH4 peptide (open circles) or BH4 mutant ΔFL peptide (filled circles) for 5 min at the indicated concentrations, followed by incubation with rBak (1 μg/μl) for 1 h. Data are indicated as mean ± SD for three independent experiments. (K) Lack of effect of Ab#20 and Ab#25 on hemolysin-induced release of hemoglobin from RBCs. RBCs, at 2.5% (vol/vol), were preincubated with Ab#20, Ab#25, or NRI at 0.8 μg/μl for 5 min, and then were incubated with Kanagawa (K) hemolysin at the indicated concentrations for 1 h. Free hemoglobin was detected at OD543 using a spectrophotometer. The total hemoglobin content was estimated after hypotonic lysis (filled triangle). Data are indicated as mean ± SD for three independent experiments.
Mentions: It has previously been reported that addition of rBax induces lysis of RBCs, and this hemolysis has been considered to be due to formation of the Bax channel on the RBC membrane (Antonsson et al. 1997). Since VDAC is also known to be located on the plasma membrane (Cole et al. 1992; Buettner et al. 2000), the possibility was raised that Bax-mediated RBC lysis was also mediated by the VDAC. The presence of the VDAC on RBC plasma membrane was confirmed by flow cytometry (Fig. 7 A), which also showed that it was oriented with the epitope for Ab#25 facing outside, consistent with previous observations (Cole et al. 1992). Since RBCs do not possess mitochondria, which was confirmed by the absence of cytochrome c (Fig. 7 B), and since they have no ER and Golgi apparatus, the VDAC shown by Western blotting (Fig. 7 B) probably largely represented VDAC on the plasma membrane. The VDAC on RBCs was ∼1 kD smaller than that in HeLa cells (Fig. 7 B), but reacted with all the anti-VDAC antibodies (31HL, Ab#25 [Fig. 7 B], Ab#20, and an antibody whose epitope was amino acids 177–192 [data not shown]), and, therefore, the VDAC on RBCs probably represents a splicing variant or is subjected to RBC-specific modifications. Several erythrocyte-specific alterations of proteins have been reported, for example, hexokinase and pyruvate kinases (Lacrinique et al. 1992; Murakami and Piomelli 1997). The possibility was not excluded that the VDAC on RBCs represents a protein highly related to VDAC or another member of the VDAC family. The presence of the VDAC on RBC plasma membrane was also confirmed by tryptic digestion of VDAC but not glyceraldehyde 3-phosphate dehydrogenase (GPDH), a cytosolic glycolytic enzyme (Fig. 7 C), and by the presence of VDAC in ghost RBCs (Fig. 7 D). Like mitochondrial VDAC, VDAC in RBCs bound to rBax (Fig. 7 E).

Bottom Line: Through direct interaction with the voltage-dependent anion channel (VDAC), proapoptotic members of the Bcl-2 family such as Bax and Bak induce apoptogenic cytochrome c release in isolated mitochondria, whereas BH3-only proteins such as Bid and Bik do not directly target the VDAC to induce cytochrome c release.When microinjected into cells, these anti-VDAC antibodies, but not control antibodies, also prevented Bax-induced cytochrome c release and apoptosis, whereas the antibodies did not prevent Bid-induced apoptosis, indicating that the VDAC is essential for Bax-induced, but not Bid-induced, apoptogenic mitochondrial changes and apoptotic cell death.Taken together, our data provide evidence that the VDAC plays an essential role in apoptogenic cytochrome c release and apoptosis in mammalian cells.

View Article: PubMed Central - PubMed

Affiliation: Osaka University Graduate School of Medicine, Biomedical Research Center, Department of Medical Genetics, Osaka 565-0871, Japan.

ABSTRACT
Through direct interaction with the voltage-dependent anion channel (VDAC), proapoptotic members of the Bcl-2 family such as Bax and Bak induce apoptogenic cytochrome c release in isolated mitochondria, whereas BH3-only proteins such as Bid and Bik do not directly target the VDAC to induce cytochrome c release. To investigate the biological significance of the VDAC for apoptosis in mammalian cells, we produced two kinds of anti-VDAC antibodies that inhibited VDAC activity. In isolated mitochondria, these antibodies prevented Bax-induced cytochrome c release and loss of the mitochondrial membrane potential (Deltapsi), but not Bid-induced cytochrome c release. When microinjected into cells, these anti-VDAC antibodies, but not control antibodies, also prevented Bax-induced cytochrome c release and apoptosis, whereas the antibodies did not prevent Bid-induced apoptosis, indicating that the VDAC is essential for Bax-induced, but not Bid-induced, apoptogenic mitochondrial changes and apoptotic cell death. In addition, microinjection of these anti-VDAC antibodies significantly inhibited etoposide-, paclitaxel-, and staurosporine-induced apoptosis. Furthermore, we used these antibodies to show that Bax- and Bak-induced lysis of red blood cells was also mediated by the VDAC on plasma membrane. Taken together, our data provide evidence that the VDAC plays an essential role in apoptogenic cytochrome c release and apoptosis in mammalian cells.

Show MeSH
Related in: MedlinePlus