This review discusses the role of brefeldin A (BFA) in understanding membrane traffic and organelle structure within the central vacuolar system of eukaryotic cells. BFA, a macrocyclic lactone, inhibits protein secretion and disrupts the Golgi apparatus, leading to the redistribution of proteins and membranes into the endoplasmic reticulum (ER). Key findings include: 1. **Inhibition of Protein Secretion**: BFA blocks protein secretion at an early step in the secretory pathway, causing secretory and membrane proteins to remain in the ER. 2. **Disassembly of the Golgi Apparatus**: BFA treatment causes the Golgi apparatus to disassemble, with Golgi enzymes appearing in the ER and Golgi markers redistributing into the ER. 3. **Membrane Tubules as Intermediates**: BFA induces the formation of membrane tubules, which extend from Golgi cisternae and microtubules. These tubules are intermediates in the movement of Golgi membrane into the ER. 4. **Retrograde Transport**: BFA enhances the retrograde transport of Golgi membrane into the ER, suggesting a normal pathway for this process. 5. ** Effects on Peripheral Organelles**: BFA also affects peripheral organelles such as endosomes, lysosomes, and the trans-Golgi network (TGN), causing tubulation and redistribution. 6. **Biochemical Changes**: BFA inhibits the binding of coat proteins (e.g., β-COP and ARF) to Golgi membranes, leading to the release of these proteins and the disassembly of the Golgi apparatus. 7. **Model of BFA Action**: The review proposes a model where BFA inhibits the assembly of coat proteins onto target membranes, leading to the disassembly of the Golgi apparatus and the formation of tubules. 8. **Homotypic and Heterotypic Membrane Traffic**: BFA distinguishes between homotypic (coated vesicle-mediated) and heterotypic (membrane budding) membrane traffic, with the former requiring coat proteins and the latter not. The review concludes by highlighting the significance of BFA studies in advancing our understanding of organelle biology and membrane traffic, and suggests that further research will continue to refine our knowledge in this area.This review discusses the role of brefeldin A (BFA) in understanding membrane traffic and organelle structure within the central vacuolar system of eukaryotic cells. BFA, a macrocyclic lactone, inhibits protein secretion and disrupts the Golgi apparatus, leading to the redistribution of proteins and membranes into the endoplasmic reticulum (ER). Key findings include: 1. **Inhibition of Protein Secretion**: BFA blocks protein secretion at an early step in the secretory pathway, causing secretory and membrane proteins to remain in the ER. 2. **Disassembly of the Golgi Apparatus**: BFA treatment causes the Golgi apparatus to disassemble, with Golgi enzymes appearing in the ER and Golgi markers redistributing into the ER. 3. **Membrane Tubules as Intermediates**: BFA induces the formation of membrane tubules, which extend from Golgi cisternae and microtubules. These tubules are intermediates in the movement of Golgi membrane into the ER. 4. **Retrograde Transport**: BFA enhances the retrograde transport of Golgi membrane into the ER, suggesting a normal pathway for this process. 5. ** Effects on Peripheral Organelles**: BFA also affects peripheral organelles such as endosomes, lysosomes, and the trans-Golgi network (TGN), causing tubulation and redistribution. 6. **Biochemical Changes**: BFA inhibits the binding of coat proteins (e.g., β-COP and ARF) to Golgi membranes, leading to the release of these proteins and the disassembly of the Golgi apparatus. 7. **Model of BFA Action**: The review proposes a model where BFA inhibits the assembly of coat proteins onto target membranes, leading to the disassembly of the Golgi apparatus and the formation of tubules. 8. **Homotypic and Heterotypic Membrane Traffic**: BFA distinguishes between homotypic (coated vesicle-mediated) and heterotypic (membrane budding) membrane traffic, with the former requiring coat proteins and the latter not. The review concludes by highlighting the significance of BFA studies in advancing our understanding of organelle biology and membrane traffic, and suggests that further research will continue to refine our knowledge in this area.