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Official Full Name
BCL2-associated X protein
This gene encodes a polypeptide hormone precursor that undergoes extensive, tissue-specific, post-translational processing via cleavage by subtilisin-like enzymes known as prohormone convertases. There are eight potential cleavage sites within the polypeptide precursor and, depending on tissue type and the available convertases, processing may yield as many as ten biologically active peptides involved in diverse cellular functions. The encoded protein is synthesized mainly in corticotroph cells of the anterior pituitary where four cleavage sites are used; adrenocorticotrophin, essential for normal steroidogenesis and the maintenance of normal adrenal weight, and lipotropin beta are the major end products. In other tissues, including the hypothalamus, placenta, and epithelium, all cleavage sites may be used, giving rise to peptides with roles in pain and energy homeostasis, melanocyte stimulation, and immune modulation. These include several distinct melanotropins, lipotropins, and endorphins that are contained within the adrenocorticotrophin and beta-lipotropin peptides. Mutations in this gene have been associated with early onset obesity, adrenal insufficiency, and red hair pigmentation. Alternatively spliced transcript variants encoding the same protein have been described.
BAX; bcl2-L-4; BCL2L4; BCL2-associated X protein; Bcl-2-associated X protein; Apoptosis regulator BAX; Bcl-2-like protein 4; OTTHUMP00000218291; OTTHUMP00000218292; OTTHUMP00000218293; OTTHUMP00000218294; OTTHUMP00000218295; OTTHUMP00000218296; BCL2-associated X protein omega

Cat.No. Product Name Price
CLKO-0033BAX KO Cell Lysate-HeLaInquiry

Apoptosis is the main type of programmed cell death in animals, participating to the modeling of organs during the development, and to tissue homeostasis during the whole life. Is activated after external or internal stimulation and leads to non-inflammatory reactions, opposite to other forms of cell death, such as necrosis. The group of proteins known as Bcl-2 family members are central players of apoptosis, because they form the interface between the early signaling events that cause cells to enter the apoptotic process and the events that later confer apoptosis characteristics to the cells, leading to their elimination by the immune system. Family members of Bcl-2 are characterized by four homologous domains, termed BH1 to BH4. Classically, the Bcl-2 family is divided into three subfamilies: anti-apoptotic proteins (e.g. Bcl-2, Bcl-xL), pro-apoptotic proteins (e.g. Bax, Bak, Bok) and only BH3 proteins (e.g. Bid, Bad).

The homologue function of Bcl-2 is critical for the regulation of mitochondrial outer membrane permeabilization (MOMP), the key event irreversibly engaging the cells towards death. After MOMP, a specific set of proteases is activated. This activation occurs through two processes: (1) procaspase is cleaved into two subunits and recombined into active heterotetramers and (2) IAPs, a family of caspases inhibitors, are inactivated. It is now widely accepted by investigators that MOMP is caused by the formation of large pores on the outer membrane of mitochondria (MOM), which enables the release of several proteins from the mitochondrial intermembrane space to the cytosol. There are five proteins have been identified as ‘apoptogenic factors’. Among the apoptogenic factors, cytochrome c is one of the most ubiquitous and conserved proteins in the whole living world, a feature most certainly related to its central function as a mobile electron carrier that shuttles between respiratory complexes. Therefore, it can be used as a universal mark for MOMP, including in model systems that do not carry out6 canonical apoptosis. Most specifically, the release of cytochrome c became a criterion in the study of the function of Bcl-2 homologs in animals after expression in yeast. The expression of human Bax was shown to promote the release of cytochrome c in yeast even before it was shown in human cells. Like in mammalian cells, several death signals in yeast, such as acetic acid treatment, induces significant mitochondrial morphological changes and non-selective release of membrane clearance proteins, which have homologies with mammalian apoptogenic factors. Interestingly, Bax effects in yeast do not depend on other proteins that are released following death stimuli, such as acetic acid treatment, that may induce a necrotic type of death depending on massive mitochondrial permeabilization resembling mPTP. This supports the view that, in mammalian cells, only cytochrome would be released through Bax-formed channels, while other apoptogenic factors would be released through other systems, such as mPTP or ceramides channels.

Fig. 1. Mitochondrial proteins released during cell death in mammals and yeast. (T.T. Renault et al. Mechanisms of Ageing and Development. 2017).

Bax retrotranslocation

It has long been believed that Bax translocation from the cytoplasm to the mitochondria is a one-way process. This came from the observation that, in non-apoptotic cells, Bax localization is essentially diffuse in the cytosol while, after apoptosis is triggered, it is relocated to mitochondria to form membrane-inserted oligomers that are responsible for MOMP. However, important observations indicate that passage from soluble/monomer Bax to membrane insertion/oligo-Bax expression is not a one-step method. For example, it has been shown that, during anoikis, Bax could be relocalized to mitochondria, but that the process was reversible. T.T. Renault et al. demonstrated that the 'mitochondrial Bax gene' is not a mandatory 'membrane insertion' Bax protein. Structural studies have allowed designing a complex Bax mutant that has a constitutive mitochondrial localization but that cannot support the conformational change associated to the oligomerization, thus remaining incompetent for cytochrome c release. When expressed in HCT-116 or in HeLa cells, the GFP-tagged form of this mutant showed mitochondrial localization and did not trigger apoptosis. After photobleaching of GFP fluorescence in the nucleus, both nuclear and cytoplasmic fluorescence disappeared, while mitochondrial fluorescence remained. This reflected the rapid dynamics of exchange between the nucleus and the cytosol, and its absence for mitochondrial Bax. However, by following the re-appearance of the fluorescence in the cytosol, the authors showed that a fraction of mitochondrial Bax could be retrotranslocated from the mitochondria to the cytosol. Most interestingly, this reverse transposition process is greatly accelerated when the anti-apoptotic protein Bcl-xl is overexpressed. This led the authors to conclude that, in non-apoptotic cells, (1) Bax subcellular localization followed a dynamic equilibrium between mitochondria and cytosol and that (2) anti-apoptotic proteins could displace this equilibrium towards a more cytosolic localization. An additional interesting observation was that a mutant of Bcl-xL deleted of the C-terminal α-helix (Bcl-xLΔC) was unable to promote Bax retrotranslocation, and further experiments demonstrated that the deletion of the last residues of Bcl-xL were sufficient to prevent it.  

Fig. 2. Comparison of the effects of full-length Bcl-xL and truncated Bcl-xLΔC on Bax mitochondrial localization. (T.T. Renault et al. Mechanisms of Ageing and Development. 2017).


  1. T.T. Renault et al. A brewing understanding of the regulation of Bax function by Bcl-xL and Bcl-2. Mechanisms of Ageing and Development. Volume 161, Part B, January 2017, Pages 201-210.
  2. Aouacheria et al. Hardwick.Evolution of Bcl-2 homology motifs: homology versus homoplasy. Trends Cell Biol. 23 (2013), pp. 103-111.
  3. Beaumatin et al. N52 monodeamidated Bcl-xL shows impaired oncogenic properties in vivo and in vitro. Oncotarget, 7 (2016), pp. 17129-17143.
  4. S. Bleicken, G. Jeschke, C. Stegmueller, R. Salvador-Gallego, A.J. García-Sáez, E. Bordignon. Structural model of active Bax at the membrane. Mol. Cell., 56 (2014), pp. 496-505.
  5. L. Große, C.A. Wurm, C. Brüser, D. Neumann, D.C. Jans, S. Jakobs. Bax assembles into large ring-like structures remodeling the mitochondrial outer membrane in apoptosis. EMBO J. 35 (2016), pp. 402-413.

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