BNIP3 - a regulator of mitochondrial autophagy and cell death

Mon, 04/13/2015 - 14:38

Bcl-2 nineteen-kilodalton interacting protein 3 (BNIP3) is a pro-apoptotic BH3-only protein. BNIP3 localizes to the mitochondrial membrane where it plays a key role in mitochondrial autophagy and cell death pathways. Similar to other Bcl-2 family members, BNIP3 binds to Bcl-2 and can activate the downstream effectors of Bax/Bak. However in contrast to the other family members, BNIP3 is a much weaker inducer of cell death and it is the transmembrane domain of BNIP3 that is responsible for this activity and not its BH3 domain. Depending on the cellular context BNIP3 can induce different forms of cell death including apoptosis, necrosis, and autophagy. BNIP3 can insert into the mitochondrial membrane and induce the opening of the mitochondrial permeability transition pore and eventually lead to necrosis. BNIP3 can also trigger the release of cytochrome c during apoptosis causing caspase dependent cell death. A hypoxia-inducible factor-1 (HIF-1)-responsive element is able to activate transcription of BNIP3 under hypoxic conditions and is important for BNIP3's role in mitochondrial autophagy. BNIP3 is also highly expressed in the poorly oxygenated environment of solid tumors. However, BNIP3 is often mis-localized or deregulated in cancer cells to overcome its cell death inducing activity.

BNIP3 antibody

Immunohistochemistry-Paraffin: BNIP3 Antibody (EPR4034) [NBP1-95586] - Analysis of paraffin-embedded human kidney tissue using anti-NIP3 / BNIP3.

During an investigation of mechanisms of rheumatoid arthritis the Knowles group examined osteoclasts in response to hypoxic conditions. They used the BNIP3 antibody to demonstrate that although induced by hypoxia at the mRNA level BNIP3 protein does not accumulate (1). This suggested a cell type specific adaptive mechanism to allow enhanced short term ATP production and bone resorption. Landes et al. discovered an interaction between BNIP3 and Opa1, a dynamin that regulates mitochondrial dynamics (2). They used the BNIP3 antibody for co-immunoprecipitation experiments to confirm the BNIP3-Opa1 interaction. They then went on to use the BNIP3 antibody to examine the effects of mutations in BNIP3 have on Opa1 complex assembly. The Weissler group of UT Southwestern used a mouse model of emphysema to examine the molecular mechanisms of cell death in lung tissue (3). They performed immunohistochemistry with the BNIP3 antibody to show increased protein levels in response to the expression of PLAG1, a hypoxia induced gene. The Seales group of UC Boulder used the BNIP3 antibody as a marker for mitophagy and mitochondrial quality control in their examination of the effects of age and diet on arterial stiffening (4).
Novus Biologicals offers BNIP3 reagents for your research needs including:


  1. 23303559
  2. 20436456
  3. 19574421
  4. 25034910

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