Article ｜ 29 Dec 2023

WIKIMOLE—Bafilomycin A1 & Rapamycin

By TargetMol

Bafilomycin A1 T6740

Bafilomycin A1, or Baf A1 for short, is a kind of macrolides antibiotic. It is a specific and reversible inhibitor of V-ATPase, and it also functions as a late-stage inhibitor of autophagy. It has the ability to block the fusion of autophagosomes with lysosomes, thereby inhibiting acidification and protein degradation within cellular lysosomes.

 

 

 

Rapamycin T1537

Rapamycin, a macrolide compound, is an effective and specific mTOR inhibitor. mTOR plays a crucial regulatory role in the autophagy process, and rapamycin induces autophagy by inhibiting mTOR. Therefore, rapamycin is commonly used as an autophagy inducer in research.

 

 

 

 

Mechanism of Action

Bafilomycin A1 disrupts the fusion of autophagosomes with lysosomes and the acidification of lysosomes, exerting an inhibitory effect on autophagy. The fusion of autophagosomes with lysosomes and the acidification of lysosomes are late-stage steps in the autophagic process, essential for maintaining functional autophagic flux and cellular homeostasis. Lysosomes are cellular organelles containing hydrolytic enzymes capable of degrading substances such as proteins, nucleic acids, and lipids. Modulating the acidic environment within lysosomes controls the efficiency and speed of their degradation.

 

Bafilomycin A1 inhibits the function of the V-ATPase within lysosomes, thereby preventing the formation of an acidic environment in lysosomes. Additionally, Baf A1 can inhibit the endoplasmic reticulum calcium ATPase Ca-P60A/SERCA, disrupting the fusion of autophagosomes with lysosomes. By acting at two steps in the autophagy, Baf A1 collectively prevents protein degradation and functional autophagy.

 

 

Biological Applications

Bafilomycin A1 is a late-stage autophagy inhibitor. Autophagy, meaning "self-eating," is the cellular process of degrading its own cytoplasmic proteins and damaged organelles using lysosomes. Autophagy serves to prevent cellular damage, promote cell survival under nutrient-deficient conditions, and respond to cytotoxic stimuli. However, excessive autophagy can lead to metabolic stress, degradation of cellular components, and even cell death. Research indicates that autophagy plays a crucial role in various physiological and pathological processes such as cellular homeostasis, aging, immunity, inflammation, tumorigenesis, and neurodegenerative diseases.

 

 

 

Reference

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