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BNIP3

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All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

Background

BNIP3 (BCL2/adenovirus E1B 19 kDa protein-interacting protein) or NIP3 is a single-pass transmembrane protein of 194-amino acids that belongs to the atypical BH3-only subfamily from the BCL-2 family with an estimated molecular weight of approximately 21.8kDa in prediction and its SDS-PAGE derived gel migration shows an apparent dimerization band at about 30–35kD due to possible post-translational modifications resulting by glycosylation, phosphorylation. In normal physiological settings, BNIP3 is mostly located in the cytoplasm without a significant monomeric activity or weakly associated with OMM and endoplasmic reticulum. Under hypoxic stress, BNIP3 is transcriptionally activated by HIF-1αthrough binding to the hypoxia response elements (HRE) in the promoter of its gene region and robust upregulation. In addition to its role in mitophagy, BNIP3 also has pro-apoptotic activity via the action of it's BH3 domain and TMD that can induce mitochondrial permeability transition (MPT), ROS production, and cytochrome c-independent cell death.

Fig.1 BNIP3 phosphorylation-mediated mitophagy under hypoxia. (OA Literature)Fig.1 The hypothetical mechanism of BNIP3 phosphorylation-mediated mitophagy under hypoxia.1

BNIP3 Protein Function: A Molecular Switch Between Survival and Death

The functional versatility of BNIP3 is due to its particular ability to combine mitochondrial quality control and programmed cell death:

  • Hypoxia-Induced Mitophagy and Metabolic Adaptation: BNIP3 is the best-studied receptor-mediated mitophagy pathway induced by hypoxic conditions. BNIP3-dependent mitophagy, through the selective removal of damaged or dysfunctional mitochondria prevents ROS accumulation, preserves cellular energy homeostasis and promotes a metabolic switch from oxidative phosphorylation to upregulation of glycolysis—classical Warburg effect in cancer cells. BNIP3-mediated mitophagy promotes metabolic reprogramming through mitochondrial respiration and inhibition of glycolysis in tumoral progression and metastasis in uveal melanoma.
  • Pro-Apoptotic Signaling and Mitochondrial Permeability Transition: In the setting of intense or chronic hypoxic stress, BNIP3 can initiate cell loss through a means that is biochemically different from classical caspase-dependent apoptosis. The BH3 domain and TMD work together to trigger MPTP opening causing mitochondrial membrane potential loss, ROS burst and necrotic cell death. The involvement of MPTP was confirmed by the inhibition of this pathway with cyclosporin A and bongkrekic acid.
  • Cancer Stem Cell Suppression and Tumor Progression: BNIP3 and its paralog NIX (BNIP3L) are recognized as negative regulators of cancer stemness. BMK1/ERK5 pathway roles in the inhibition of BNIP3 and NIX induction to regulate tumor stem cell drawbacks through autophagy-mediated regulatory mechanism. On the other hand, mitophagy defects resulting from loss of BNIP3 promote mammary tumor metastasis progression thereby underscoring a context-dependent role for BNIP as both a suppressor (by inhibiting stem cell activity) and promotor (via metabolic reprogramming) in tumorgenesis.

BNIP3 Membrane Protein Product

We offer high-quality BNIP3 membrane protein products designed to support structural and functional studies of this mitophagy-related protein. Our Membrane Protein Platform provides BNIP3 constructs and preparations suitable for a range of research applications, including antibody development and characterization, binding studies, protein–protein interaction analysis, and investigation of BNIP3-related mitophagy and apoptosis mechanisms. These products can support studies of BNIP3 interactions with LC3, BCL-2, Beclin-1, and other components of autophagy-related pathways. Available formats and construct designs may vary according to specific research requirements, with appropriate quality assessment applied based on the intended application.

BNIP3 Protein Product

Not finding the membrane protein product you need? Contact us to start your one-stop custom service!

BNIP3 Stable Cell Line Product

BNIP3 research requires robust cellular models. Our stable cell lines are designed to support mitophagy studies, hypoxia-response research, metabolic investigations, and compound screening related to BNIP3 biology. Leveraging our cell engineering expertise, we provide customized BNIP3 stable expression or regulation models according to specific experimental requirements. These cell models can support gain- or loss-of-function studies and the investigation of BNIP3-mediated mitophagy, metabolic reprogramming, and hypoxia-related signaling. Appropriate expression and functional characterization strategies can be selected based on the intended research application.

BNIP3 Stable Cell Line Product

Not finding the stable cell line product you need? Contact us to start your one-stop custom service!

BNIP3 Recombinant Antibody Product

We have developed a portfolio of recombinant antibodies against BNIP3 for a range of research applications. Recombinant production supports consistent reagent supply and lot-to-lot reproducibility for routine research use. Depending on the specific product and supporting datasheet, BNIP3 recombinant antibodies may be suitable or available for selected applications such as Western Blotting (WB), ELISA, Flow Cytometry (FCM), Immunofluorescence (IF), Immunocytochemistry (ICC), and Immunohistochemistry (IHC). These antibodies can support the detection and analysis of BNIP3 expression and related biological processes in appropriate research samples and model systems. For studies requiring recognition of specific BNIP3 regions or other specialized antibody properties, customized antibody development and suitability assessment can be discussed according to the intended experimental design.

BNIP3 Recombinant Antibody Product

Not finding the recombinant antibody product you need? Contact us to start your one-stop custom service!

Product Features

  • High Purity & Activity: High purity and verified integrity for dependable downstream work.
  • Diverse Expression Systems: Choice of expression formats to match routine or specialized projects.
  • Species Reactivity: Products available for human, mouse, pig, and other species.
  • Validated Applications: Application-tested to deliver consistent signals across common lab workflows.
  • Superior Batch-to-Batch Consistency: Stringent quality controls to ensure low variability from batch to batch.
  • Customization Options: Tags/Labels/package Modifications available upon request.

Custom BNIP3 Membrane Protein and Antibody Discovery Services

In addition to our catalog products, Creative Biolabs provides high-performing customized services, including but not limited to membrane protein and antibody discovery & development. With this background and our next-generation platforms, we can help you with:

  • Production & Validation: Cloning of the synthesized optimized gene into an expression vector, plus small-scale expression trials to help determine the best expression conditions.
  • Custom Antibody Production: Produced via large-scale expression in mammalian/insect/cell culture or bacterial expression systems, purified in detergent or reconstituted into nanodiscs.
  • Engineered Cell Lines: Creation of stable cell lines that physiologically mimic endogenous BNIP3 expression and activity.
  • Functional Assessment Systems: Designing and executing assays to assess protein function and ligand binding.

Frequently Asked Questions (FAQ)

  1. Can Creative Biolabs generate BNIP3 variants for mitophagy and apoptosis studies?

    Absolutely. We provide custom protein engineering services for various mutations, such as phosphorylation-mimetic mutants (S17E/S24E/S60E/T66E), LIR-deficient (W18A/L21A) and dimerization-disrupting based on GxxxG substitutions in the TMD replacements, BH3 domain truncations, PEST domain deletions. tag fusions since TMBD-His/Hii6/FAB-FLAG/GFP/biotin /formulation specificizations. We work with our scientific team to help clients develop constructs for structural biology, interaction mapping and therapeutic screening.

  2. Are your reagents for BNIP3 cleared as clinical diagnostic tests to predict major loss of hypoxic endogenous biomarkers such as damage, and how well patients stratify prognostically?

    No, all reagents and services are only for research use and shall not be used in diagnosing or treating disease.

  3. Do you offer stable cell lines with tetracycline-inducible BNIP3 expression for temporal modeling of hypoxia-mimetic mitophagy initiation, mitochondrial network fragmentation, and subsequent cell death commitment?

    Yes, we have generated stable lines in which BNIP3 transcription is dependent on a tetracycline responsive promoter. Such a setup allows for highly controlled initiation of expression at predetermined time points, followed by measurements of subsequent mitochondrial depolarization kinetics, Parkin-independent mitophagosome formation and caspase-independent cell death with temporal resolution that is freed from the variabilities associated with transient transfection or hypoxia mimetic compounds.

  4. What types of BNIP3 products does Creative Biolabs offer?

    We have a broad portfolio of products including recombinant BNIP3 membrane proteins, in different formats (detergent-solubilized / liposome-reconstituted / mitochondria-enriched fractions), stable cell lines expressing the BNIP3 protein (overexpressing/knockdown/reporter line; high-affinity recombinant BTN antibodies that bind distinct epitopes and phosphorylation sites, and fully customized for engineering services for new protein and antibody discovery. We have mouse, rat and other mammalian species products.

Reference
  1. He, Yun-Ling, et al. "BNIP3 phosphorylation by JNK1/2 promotes mitophagy via enhancing its stability under hypoxia." Cell Death & Disease 13.11 (2022): 966. Under Open Access license CC BY 4.0, without modification. https://doi.org/10.1038/s41419-022-05418-z
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