Direct measurement of VDAC–actin interaction by surface plasmon resonance

Roman, Inge; Figys, Jurgen; Steurs, Griet; Zizi, Martin

doi:10.1016/j.bbamem.2006.03.019

Cited by 41 publications

(29 citation statements)

References 49 publications

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“…G-actin directly and selectively binds to VDAC in yeast, as demonstrated by surface plasmon resonance [371]. Moreover, the monomeric form of G-actin could modulate gating of the Neurospora crassa VDAC channel by reducing its conductance [298].…”

Section: Interaction Of Vdac1 With and Regulation By Cytoskeletal Promentioning

confidence: 98%

The mitochondrial voltage-dependent anion channel 1 in tumor cells

Shoshan‐Barmatz

Ben-Hail

Admoni

et al. 2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

212

254

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VDAC1 is found at the crossroads of metabolic and survival pathways. VDAC1 controls metabolic cross-talk between mitochondria and the rest of the cell by allowing the influx and efflux of metabolites, ions, nucleotides, Ca2+ and more. The location of VDAC1 at the outer mitochondrial membrane also enables its interaction with proteins that mediate and regulate the integration of mitochondrial functions with cellular activities. As a transporter of metabolites, VDAC1 contributes to the metabolic phenotype of cancer cells. Indeed, this protein is over-expressed in many cancer types, and silencing of VDAC1 expression induces an inhibition of tumor development. At the same time, along with regulating cellular energy production and metabolism, VDAC1 is involved in the process of mitochondria-mediated apoptosis by mediating the release of apoptotic proteins and interacting with anti-apoptotic proteins. The engagement of VDAC1 in the release of apoptotic proteins located in the inter-membranal space involves VDAC1 oligomerization that mediates the release of cytochrome c and AIF to the cytosol, subsequently leading to apoptotic cell death. Apoptosis can also be regulated by VDAC1, serving as an anchor point for mitochondria-interacting proteins, such as hexokinase (HK), Bcl2 and Bcl-xL, some of which are also highly expressed in many cancers. By binding to VDAC1, HK provides both a metabolic benefit and apoptosis-suppressive capacity that offer the cell a proliferative advantage and increase its resistance to chemotherapy. Thus, these and other functions point to VDAC1 as an excellent target for impairing the re-programed metabolism of cancer cells and their ability to evade apoptosis. Here, we review current evidence pointing to the function of VDAC1 in cell life and death, and highlight these functions in relation to both cancer development and therapy. In addressing the recently solved 3D structures of VDAC1, this review will point to structure-function relationships of VDAC as critical for deciphering how this channel can perform such a variety of roles, all of which are important for cell life and death. Finally, this review will also provide insight into VDAC function in Ca2+ homeostasis, protection against oxidative stress, regulation of apoptosis and involvement in several diseases, as well as its role in the action of different drugs. We will discuss the use of VDAC1-based strategies to attack the altered metabolism and apoptosis of cancer cells. These strategies include specific siRNA able to impair energy and metabolic homeostasis, leading to arrested cancer cell growth and tumor development, as well VDAC1-based peptides that interact with anti-apoptotic proteins to induce apoptosis, thereby overcoming the resistance of cancer cell to chemotherapy. Finally, small molecules targeting VDAC1 can induce apoptosis. VDAC1 can thus be considered as standing at the crossroads between mitochondrial metabolite transport and apoptosis and hence represents an emerging cancer drug target. This article is part of a Special ...

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Section: Interaction Of Vdac1 With and Regulation By Cytoskeletal Promentioning

confidence: 98%

The mitochondrial voltage-dependent anion channel 1 in tumor cells

Shoshan‐Barmatz

Ben-Hail

Admoni

et al. 2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

212

254

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“…Interactions of VDAC with other proteins, including creatine kinase (19), cytochrome c (20), the benzodiazepine receptor (21), the adenine nucleotide translocator (22), actin (23), and the mtHSP70 heat shock protein have also been proposed. VDAC is proposed to be a critical component of the mitochondrial phase of apoptosis, with its interaction with Bcl-2 family proteins and controlling the rate of release of intermembrane space proteins that activate the execution phase of apoptosis (10).…”

mentioning

confidence: 99%

Hexokinase-I Protection against Apoptotic Cell Death Is Mediated via Interaction with the Voltage-dependent Anion Channel-1

Abu-Hamad

Zaid

Israelson

et al. 2008

Journal of Biological Chemistry

236

268

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In brain and tumor cells, the hexokinase isoforms HK-I and HK-II bind to the voltage-dependent anion channel (VDAC) in the outer mitochondrial membrane. We have previously shown that HK-I decreases murine VDAC1 (mVDAC1) channel conductance, inhibits cytochrome c release, and protects against apoptotic cell death. Now, we define mVDAC1 residues, found in two cytoplasmic domains, involved in the interaction with HK-I. Protection against cell death by HK-I, as induced by overexpression of native or mutated mVDAC1, served to identify the mVDAC1 amino acids required for interaction with HK-I. HK-I binding to mVDAC1 either in isolated mitochondria or reconstituted in a bilayer was inhibited upon mutation of specific VDAC1 residues. HK-I anti-apoptotic activity was also diminished upon mutation of these amino acids. HK-I-mediated inhibition of cytochrome c release induced by staurosporine was also diminished in cells expressing VDAC1 mutants. Our results thus offer new insights into the mechanism by which HK-I promotes tumor cell survival via inhibition of cytochrome c release through HK-I binding to VDAC1. These results, moreover, point to VDAC1 as a key player in mitochondrially mediated apoptosis and implicate an HK-I-VDAC1 interaction in the regulation of apoptosis. Finally, these findings suggest that interference with the binding of HK-I to mitochondria by VDAC1-derived peptides may offer a novel strategy by which to potentiate the efficacy of conventional chemotherapeutic agents.Accumulating evidence indicates that the mitochondrially bound isoforms of hexokinase, HK-I and HK-II, play pivotal roles in promoting cell growth and survival in rapidly growing, highly glycolytic tumors (1). As such, HK-I and HK-II were found to be overexpressed in many types of cancer, including colon, prostate, lymphoma, glioma, gastric adenomas, carcinomas, and breast cancers (2-5). The elevated levels of HK-I and HK-II allow tumor cells to evade apoptosis, thereby allowing proliferation to continue (6, 7). HK-I and HK-II dock onto the cytosolic surface of the outer mitochondrial membrane mainly through binding to the voltage-dependent anion channel (VDAC) 4 (8). It has been proposed that binding of HK to mitochondria allows a continuous ATP flux, providing energy for the phosphorylation of glucose, and thus an increased glycolytic rate (7). VDAC, also known as mitochondrial porin, functions as the major channel allowing passage of nucleotides, ions, Ca 2ϩ , and other metabolites between the intermembrane space and cytoplasm (9 -11).In vitro and in vivo studies have shown that HK-I and HK-II play a clear role in protecting against mitochondrially regulated apoptosis through direct interaction with mitochondria (3) and, more specifically, with VDAC (6). Several recent studies demonstrated that in tumor cells, HK-I (12-14) and HK-II (15, 16) not only augment cellular energy supply and levels of glucose 6-phosphate, an intermediate metabolic in many biosynthetic pathways, but also protect against cell death. The molecular mechanisms by...

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“…Purified VDAC1 interacts with a cytoplasmic dynein light chain Tctex-1 in vitro (Schwarzer et al, 2002). Recently, VDAC proteins were shown to interact with tubulin and actin based on immunoprecipitation and surface plasmon resonance technology (Carré et al, 2002;Roman et al, 2006). Interestingly, several kinesin receptors were identified as binding to mitochondria, such as syntabulin, kinectin, and milton (Stowers et al, 2002;Santama et al, 2004;Cai et al, 2005).…”

Section: Kp1 Specifically Interacts With the Mitochondrial Outer Membmentioning

confidence: 99%

“…It is well known that the membrane permeability of mitochondria is mainly dependent on the voltage-dependent anion channel (VDAC) (also named as a porin), the most abundant integral membrane protein in the mitochondrial outer membrane (Benz, 1994;Colombini, 1979;Liu and Colombini, 1992). Recently, both tubulin and actin from human and yeast (Saccharomyces cerevisiae) cells were found to interact with VDACs (Carré et al, 2002;Roman et al, 2006). In vitro reconstitution studies demonstrated that fungal VDACs have two main conductance states: an open state that allows the diffusion of large metabolites, including nucleotides, and a closed state that regulates ATP flux through the membrane (Rostovtseva and Colombini, 1996).…”

Section: Introductionmentioning

confidence: 99%

ArabidopsisKinesin KP1 Specifically Interacts with VDAC3, a Mitochondrial Protein, and Regulates Respiration during Seed Germination at Low Temperature

Yang

Chen

et al. 2011

The Plant Cell

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The involvement of cytoskeleton-related proteins in regulating mitochondrial respiration has been revealed in mammalian cells. However, it is unclear if there is a relationship between the microtubule-based motor protein kinesin and mitochondrial respiration. In this research, we demonstrate that a plant-specific kinesin, Kinesin-like protein 1 (KP1; At KIN14 h), is involved in respiratory regulation during seed germination at a low temperature. Using in vitro biochemical methods and in vivo transgenic cell observations, we demonstrate that KP1 is able to localize to mitochondria via its tail domain (C terminus) and specifically interacts with a mitochondrial outer membrane protein, voltage-dependent anion channel 3 (VDAC3). Targeting of the KP1-tail to mitochondria is dependent on the presence of VDAC3. When grown at 48C, KP1 dominant-negative mutants (TAILOEs) and vdac3 mutants exhibited a higher seed germination frequency. All germinating seeds of the kp1 and vdac3 mutants had increased oxygen consumption; the respiration balance between the cytochrome pathway and the alternative oxidase pathway was disrupted, and the ATP level was reduced. We conclude that the plantspecific kinesin, KP1, specifically interacts with VDAC3 on the mitochondrial outer membrane and that both KP1 and VDAC3 regulate aerobic respiration during seed germination at low temperature.

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Direct measurement of VDAC–actin interaction by surface plasmon resonance

Cited by 41 publications

References 49 publications

The mitochondrial voltage-dependent anion channel 1 in tumor cells

The mitochondrial voltage-dependent anion channel 1 in tumor cells

Hexokinase-I Protection against Apoptotic Cell Death Is Mediated via Interaction with the Voltage-dependent Anion Channel-1

ArabidopsisKinesin KP1 Specifically Interacts with VDAC3, a Mitochondrial Protein, and Regulates Respiration during Seed Germination at Low Temperature

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