Bafilomycin A1 – Potent V-ATPase Inhibitor

V-ATPase, or vacuolar-type ATPase, is essential for the function of all eukaryotic cells. It is a large protein complex that pumps protons across the membranes of intracellular organelles and the plasma membrane. This creates a proton gradient, which is used to power a variety of cellular processes, including protein folding, vesicular transport, and acidification of organelles.

As it promotes the acidification of lysosomes, endosomes, and secretory vesicles, V-ATPase contributes to processes including vesicular/protein trafficking, receptor recycling, endocytosis, protein degradation, autophagy and cell signaling. With its role in lysosomal acidification, V-ATPase is also crucial in driving the transport of ions and small molecules into the cytoplasm, particularly calcium and amino acids. Additionally, its acidification of endosomes is critical in receptor endocytosis as low pH tends to drive ligand release as well as receptor cleavage which contributes to signaling events, such as through the release of the intracellular domain of Notch. In certain specialized cells, such as neurons, V-ATPase contributes to the storage of neurotransmitters within vesicles, which are released upon neuronal signaling. Mutations in V-ATPase genes can lead to a variety of diseases, including kidney disease, lysosomal storage disorders and neurodegenerative diseases.

V-ATPases are composed of two major subcomplexes (see Figure): the peripheral V1 complex and the integral membrane VO complex. The V1 complex is located on the cytoplasmic side of the membrane and contains the ATP-binding and hydrolysis sites. The VO complex is embedded in the membrane and contains the proton channel. When ATP is hydrolyzed by the V1 complex, it releases energy that is used to pump protons across the membrane. 

Bafilomycin A1

The bafilomycins are a family of macrolide antibiotics produced from a variety of Streptomycetes. Their chemical structure is defined by a 16-membered lactone ring scaffold. Bafilomycins exhibit a wide range of biological activity, including anti-tumor, anti-parasitic, anti-viral,  immunosuppressant and anti-fungal activity.

Bafilomycin A1 is a highly potent, selective inhibitor of vacuolar H+-ATPases. Bafilomycin A1 is a potent inhibitor of cellular autophagy either by blocking autophagosome-lysosome fusion or by blocking lysosomal degradation. Autophagy is the process by which the cell degrades its own organelles and some proteins through the formation of autophagosomes. Autophagosomes then fuse with lysosomes facilitating the degradation of engulfed cargo by lysosomal proteases. This process is critical in maintaining the cell's store of amino acids and other nutrients during times of nutrient deprivation or other metabolic stresses. Bafilomycin interferes with this process by inhibiting the acidification of the lysosome through its interaction with V-ATPase. Lack of lysosomal acidification prevents the activity of lysosomal proteases like cathepsins so that engulfed cargo can no longer be degraded.

Bafilomycin A1 has been described to have several other biological activities. It was found to induce apoptosis or to act as an ionophore, meaning it can transfer K+ ions across biological membranes. Bafilomycin A1 treatment can induce mitochondrial swelling in the presence of K+ ions, stimulate the oxidation of pyrimidine nucleotides and uncouple oxidative phosphorylation. Inhibition of V‐ATPase activity with bafilomycin A1 led to the exacerbation of NLRP3 inflammasome activation in human monocytes in response to LPS. Bafilomycin A1 also significantly inhibited SARS-CoV-2 replication.

Bafilomycin A1 has been shown to have a variety of potential therapeutic benefits. In cancer, bafilomycin A1 has been shown to inhibit the growth of tumor cells by blocking the acidification of lysosomes. Lysosomes are organelles that contain enzymes that can break down tumor cells. By blocking the acidification of lysosomes, bafilomycin A1 prevents these enzymes from being activated, which can help to kill tumor cells. In lysosomal storage disorders, bafilomycin A1 has been shown to promote the clearance of accumulated cellular waste from lysosomes. This can help to improve the symptoms of lysosomal storage disorders, such as Gaucher disease and Niemann-Pick disease. In neurodegenerative diseases, bafilomycin A1 has been shown to protect neurons from damage, which helps to slow down the progression of diseases such as Alzheimer's disease and Parkinson's disease.

Literature References:

1. Bafilomycins: a class of inhibitors of membrane ATPases from microorganisms, animal cells, and plant cells: E.J. Bowman, et al.; PNAS 85, 7972 (1988)
2. Bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPase, inhibits acidification and protein degradation in lysosomes of cultured cells: T. Yoshimori, et al.; J. Biol. Chem. 266, 17707 (1991)
3. Bafilomycin A1 induces caspase-independent cell death in hepatocellular carcinoma cells via targeting of autophagy and MAPK pathways: Y. Yan, et al.; Sci. Rep. 6, 37052 (2016)
4. Molecular basis of V-ATPase inhibition by bafilomycin A1: R. Wang, et al.; Nat. Commun. 12, 1782 (2021)
5. Bafilomycin A1 enhances NLRP3 inflammasome activation in human monocytes independent of lysosomal acidification: S. Yu, et al.; FEBS J. 288, 3186 (2021)
6. Bafilomycin A1 inhibits SARS-CoV-2 infection in a human lung xenograft mouse model: C. Zhang, et al.; Virol. J. 20, 18 (2023)

Bafilomycin A1 (high purity)

Bafilomycin A1 is a macrolide antibiotic. It is a specific vacuolar-type H+-ATPase inhibitor that distinguishes among different types of ATPases. It is used as an inhibitor of endosomal, lysosomal and vacuolar acidification.

AG-CN2-2001  (100 µg, 1 mg, 5 mg and BULK)

AdipoGen Life Sciences is an original Manufacturer of Bafilomycin A1. BULK quantities are available from Stock!

Product Specifications: CAS:        88899-55-2 Source:   Isolated from Streptomyces griseus Purity:     >98% HPLC Identity:  Determined by 1H-NMR Contact us at info@adipogen.com and inquire about BULK Pricing!

Concanamycins - Potent & Selective V-ATPase Inhibitors

Concanamycins are another class of macrolide antibiotics. Like bafilomycins, concanamycins are known for their ability to potently inhibit the vacuolar-type H+-ATPase (V-ATPase). Recently, concanamycin A was shown to reverse the downregulation of cell surface MHC-I by the HIV-encoded accessory protein Nef, suggesting a possible therapeutic role of concanamycin A in enhancing the immune-mediated clearance of HIV-infected cells.