Bafilomycin A1 - Endosomal Acidification Inhibitor

Endosomal acidification and autophagy inhibitor

Bafilomycin A1 (BafA1), a macrolide antibiotic isolated from Streptomyces species, is a specific vacuolar H⁺ ATPase (V-ATPase) inhibitor. Notably, due to its ability to specifically target V-ATPase and hence disrupt autophagic flux, BafA1 is frequently used to study autophagy and endosomal acidification. Autophagy is one of the three principal mechanisms used by cells to sequester, remove and recycle waste, the others being proteasomal degradation and phagocytosis. BafA1 suppresses the growth of a variety of cancer cells by inhibiting autophagy and inducing apoptotic cell death via various mechanisms [1, 2]. Inhibition of autophagy by BafA1, in combination with anti-cancer therapies (e.g. chemotherapy), represents a promising therapeutic approach that is currently being tested in clinical trials [1].

More details

Mode of action:

By inhibiting V-ATPase, BafA1 prevents the maturation of autophagic vacuoles by inhibiting late-stage fusion between autophagosomes and lysosomes as well as lysosomal degradation [3]. V-ATPases establish and maintain a low luminal pH in endocytic and exocytic compartments. Upon binding to the V-ATPase complex BafA1 inhibits H⁺ translocation, thereby depriving acidic intracellular compartments (i.e. endosomes, lysosomes, and vesicles) of H⁺ ions, increasing their pH and inhibiting the function of resident hydrolases. On the other hand, this causes an accumulation of H⁺ in the cytoplasm of treated cells, leading to acidosis and thus, can cause secondary adverse effects in normal cells [1].

Key features:

• Specific and potent V-ATPase inhibitor frequently used to study autophagy
• InvitroFit™ grade: highly pure (> 90%) and inhibitory function validated in cellular assays

Read our review on Autophagy and Innate Immunity

References

1. Yan, Y. et al. 2016. Bafilomycin A1 induces caspase-independent cell death in hepatocellular carcinoma cells via targeting of autophagy and MAPK pathways. Sci Rep 6, 37052.
2. Yuan, N. et al. 2015. Bafilomycin A1 targets both autophagy and apoptosis pathways in pediatric B-cell acute lymphoblastic leukemia. Haematologica 100, 345-356.
3. Yamamoto, A. et al. 1998. Bafilomycin A1 prevents maturation of autophagic vacuoles by inhibiting fusion between autophagosomes and lysosomes in rat hepatoma cell line, H-4-II-E cells. Cell Struct Funct 23, 33-42.