VDAC3 Antibodies

Voltage-dependent anion-selective channel protein 3 (VDAC3)

Forms a channel through the mitochondrial outer membrane that allows diffusion of small hydrophilic molecules. .

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Gene Information

Human
Gene Name:	VDAC3
Uniprot:	Q9Y277
Entrez:	7419

Family

Belongs to:
eukaryotic mitochondrial porin family

Alternative Names

HD-VDAC3; hVDAC3; Outer mitochondrial membrane protein porin 3; VDAC-3; voltage-dependent anion channel 3; voltage-dependent anion-selective channel protein 3

Molecular Weight

Mass (kDA):
30.659 kDA

Genomic Context

Human
Location:	8p11.21
Sequence:	8; NC_000008.11 (42391624..42405937)

Tissue Specificity

Widely expressed. Highest in testis.

Subcellular Localizations

Mitochondrion outer membrane.

Diseases

• Malignant Neoplasms
• Neoplasms
• Male Infertility
• Liver Carcinoma
• Hepatitis B
• Infertility
• Carcinoma
• Hepatitis
• Malignant Paraganglionic Neoplasm
• Liver Neoplasms
• Liver Diseases
• Papilloma
• Down Syndrome

• Hypoxia
• Pre-eclampsia
• Carcinogenesis
• Fetal Growth Retardation
• Parkinson Disease
• Edema
• Exanthema

Interacting Proteins

• VDAC1

Pathways

• Cell Death
• Localization
• Transport
• Sperm Motility
• Oxidative Phosphorylation
• Mitosis
• Rna Interference
• Protein Phosphorylation
• Programmed Cell Death
• Pollen Development
• Aerobic Respiration
• Aging
• Proteolysis

• Chromosome Separation
• Mitochondrial Depolarization
• Reflex
• Cytokinesis
• Glucose Homeostasis
• Cellular Respiration
• Flight

PTMs

• Phosphorylation
• Nitrosylation

• Cleavage
• Ubiquitination

For details, visit:
bosterbio.com/bosterbio-gene-info-cards/VDAC3

Best Uses of the VDAC3 Marker in Cancer Research

The role of VDAC3 is important in cancer research, as it is involved in over-oxidation of cysteine. But what does the VDAC3 marker mean? In this article, we'll discuss its role in cancer and ciliopathies, as well as its use as an oxidative load marker for mitochondria. Let's dive in! Read on to discover the best uses of VDAC3 in cancer research.

HBx interaction

Recent studies have indicated that HBx interacts with the mitochondrial VDAC3 marker. This interaction may prevent Bcl-2 from modulating the activity of this channel. The association between HBx and VDAC3 may have important implications for the underlying biology of human herpes virus infection. A virus that causes herpes, the HHV-8, has a protein that binds to the mitochondrial VDAC3 marker.

Over-oxidation of exposed cysteines of VDAC3 in mammals has been linked to the high concentration of ROS in the IMS. These oxidative modifications are involved in molecular mechanisms for damaged mitochondria identification. Damaged mitochondria are those that are unable to produce enough ATP and display an accumulation of ROS. Cysteine oxidations of VDAC3 alter the electrostatic map of the protein, affecting its presentation to other compartments.

HBx is often studied as a transcription factor. Although a wide variety of transcriptional factors and elements have been identified as possible targets, most evidence indicates that it is predominantly cytoplasmic. Very little HBx has been found in the nucleus. Despite the importance of HBx for immune system function, the interaction of HBx and VDAC3 has yet to be fully characterized.

While it is not entirely clear exactly how HBx affects the function of VDAC3, we have shown that it stimulates the activity of several cellular systems. Furthermore, this protein can activate transcription factors such as STAT-3 and NF-kB. However, this interaction has been suggested to involve other crucial pathways that are critical for the survival of human cells. So what is the mechanism behind the HBx-VDAC3 interaction?

Despite the fact that both HBx and VDAC3 have a common N-terminal cysteine residue, there is still no conclusive proof that they are functionally equivalent. Because of the lack of a Cys2 at the N-terminus, VDAC3 may be able to follow the same degradation pathway as the other isoforms. This is the only way to determine which of the three proteins is most functionally equivalent.

Cysteine over-oxidation

The best uses of the VDAC3 marker for cystine over-oxidation are still not clear. It may be related to its ability to detect cysteine oxidation in cells and in the context of biological function. The VDAC3 gene encodes a protein that is found in mitochondria. This protein contains conserved cysteines facing the IMS. The oxidation of cysteine might result from the balance of reduction and oxidation reactions that occur in the IMS. In some situations, the oxidation of cysteines may be counterbalanced by redox-restoring systems that maintain the redox level.

The hVDAC3 gene encodes a protein with higher levels of cysteine residues than the human VDAC1 gene. Its structural model shows that four of the six cysteines are located in loops connecting the b-strands, while the N-terminal tail is present within the pore. Cys2 is oriented toward the intermembrane space, whereas Cys4 is located in the b-strand.

The protein has a peculiar migration pattern in gels without reducing agent. The single mutant, C122A, had several bands with different apparent Mr, one of which correlated with a dimer. Deleting two or three cysteines restored homogeneous electrophoretic migration. Furthermore, deleting three cysteines reduced protein aggregation. The protein also displayed decreased redox activity.

A new marker for cysteine over-oxidation has been developed to identify adenine disulfide bridge between cysteines 2 and 8 in mitochondrial proteins. The VDAC3 marker for cysteine over-oxidation provides a sensitive and precise measure of cysteine over-oxidation. It is a valuable tool for researchers, biochemists, and pharmacologists.

The mutations of the C2,8A and C2,122A mutants of VDAC3 exhibit voltage-dependent behavior. The wtVDAC3 channel and its mutants have different conductance values and ability to complement yeast. In figure 4, the representative single-channel behavior of wtVDAC3 and the individual Cys-mutants is displayed. The C2A mutation results in a higher single-channel conductance.

The best uses of the VDAC3 marker for cystosine over-oxidation are related to the detection of disulfide-based sulfhydryl oxidase-mediated reactions in the mitochondria. This marker is useful in both eukaryotes and bacteria. For research in cysteine over-oxidation, the VDAC3 gene is an ideal tool to use.

Role in ciliopathies

The VDAC3 gene is a central regulator of ciliary assembly, disassembly, and retraction. It has been associated with a variety of ciliopathies, including ciliary dysplasia, microcephaly, and tumours. It is crucial to understand how ciliary disassembly and retraction are regulated to identify potential therapeutic targets.

CENPF is a ciliary protein that localizes at the base of the cilia during quiescence and interacts with two other proteins, CEP290 and ATF4, which play a role in regulating the activity of APC/C-CDC20. These two proteins are localized at the ciliary TZ during G0/G1 phases. Mutations in these proteins cause ciliopathies.

The MCC-CDC20 complex is another ciliary-specific protein that plays an important role in cell disassembly. It has been shown that MCC downregulates APC/C-CDC20 activity. The expression of MCC may be a therapeutic target for ciliopathies. However, further research is needed to determine whether the VDAC3 gene is present in cilia.

The researchers also identified the VDAC3 interacting protein, a novel marker of the ciliary cell's centriole. However, there was a lack of reliable antibodies for identifying the VDAC3 interacting protein, and most of the information they had on VDACs is derived from general proteomic surveys. These analyses often reveal that altered levels of VDACs play a role in certain pathologies.

It is unknown whether PLK1 contributes to ciliary resorption. However, it is essential for maintaining a pool of neural progenitor cells. It also forms a scaffold for AURKA, NDE1, and OFD1 proteins. It is also required for centriole duplication in late mitosis. In addition, CENPJ promotes ciliogenesis, and its expression decreases after ciliary disassembly.

Since this gene has been involved in the ER redox system, it can be implicated in neurodegenerative diseases and aging. In addition to ciliopathies, VDAC3 also has been implicated in Parkinson's disease and myopathies. The gene is closely linked to neurodegenerative disorders, including Alzheimer's, Parkinson's, and Alzheimer's disease. Therefore, the role of VDAC3 in ciliopathies remains uncertain.

Application as a marker for oxidative load in mitochondria

Until now, little has been known about the role of N-lactoyl-amino acids, also known as a-hydroxybutyrate, in mitochondrial disease. Previously, this compound has not been associated with disease, although its elevated levels were reported in a mouse model of MELAS. This study shows that elevated levels of a-hydroxybutyrate correlate with increased hepatic NADH/NAD+ ratio, a marker of mitochondrial dysfunction.

PDK4 inhibits the pyruvate dehydrogenase complex, which converts pyruvate to acetyl-CoA. UQCRC1 catalyzes the transfer of electrons from ubiquinol to cytochrome c. This oxidative stress response in mitochondria is associated with the cellular response to apoptosis.

Although acylcarnitines are elevated in many mitochondrial disorders, only a few of them have been properly identified and quantified. For MELAS, there was a consistent pattern of acylcarnitines, including 3 hydroxy-acylcarnitines. Nevertheless, the oxidative load was too high for the complete acylcarnitine signature to be identified. However, patients with MELAS were already taking carnitine and a mitochondrial vitamin cocktail, but no creatine.

MitoSOX(tm) Red is a cationic derivative of dihydroethidium that selectively targets mitochondria. The indicator is captured in active mitochondria by electrophoresis. It then intercalates with mitochondrial DNA to produce a red fluorescence. The authors conclude that MitoSOX(tm) Red is a viable marker of mitochondrial oxidative load.

The presence of MELAS is a dynamic indicator of oxidative stress in mitochondria, with the ratio of oxidized glutathione to reduced glutathione a useful indicator of oxidative stress. Researchers who want to measure the levels of MELAS have several options for measuring the concentrations of GSH and GSSG. There are also a number of methods to measure their levels biochemically in microplates.

Despite the widespread occurrence of reactive oxygen species in humans, it is not fully understood how these molecules are produced. They are byproducts of electron transport in the mitochondria and necessary intermediates in metal-catalyzed oxidation reactions. The atomic structure of atom oxygen makes it vulnerable to radical formation and the subsequent reduction of oxygen results in a number of ROS, including hydrogen peroxide, superoxide, and hydroxyl ion.