Cannabidiol activates PINK1-Parkin-dependent mitophagy and mitochondrial-derived vesicles

European Journal of Cell Biology

William Old¹  Xuedong Liu¹  David L. Selwood²  Adrian Ramirez² 

[1] Department of MCD-Biology, University of Colorado, Boulder, CO 80309, USA;Department of Biochemistry, University of Colorado, Boulder, CO 80303, USA;

关键词: Cannabidiol;    Mitochondrial-derived vesicles (MDV);    Mitophagy;    Mitochondrial quality control;    Parkin;    PINK;   

DOI  :  

来源: DOAJ

【 摘 要 】

The PINK1/Parkin pathway plays an important role in maintaining a healthy pool of mitochondria. Activation of this pathway can lead to apoptosis, mitophagy, or mitochondrial-derived vesicle formation, depending on the nature of mitochondrial damage. The signaling by which PINK/Parkin activation leads to these different mitochondrial outcomes remains understudied. Here we present evidence that cannabidiol (CBD) activates the PINK1-Parkin pathway in a unique manner. CBD stimulates PINK1-dependent Parkin mitochondrial recruitment similarly to other well-studied Parkin activators but with a distinctive shift in the temporal dynamics and mitochondrial fates. The mitochondrial permeability transition pore inhibitor cyclosporine A exclusively diminished the CBD-induced PINK1/Parkin activation and its associated mitochondrial effects. Unexpectedly, CBD treatment also induced elevated production of mitochondrial-derived vesicles (MDV), a potential quality control mechanism that may help repair partial damaged mitochondria. Our results suggest that CBD may engage the PINK1-Parkin pathway to produce MDV and repair mitochondrial lesions via mitochondrial permeability transition pore opening. This work uncovered a novel link between CBD and PINK1/Parkin-dependent MDV production in mitochondrial health regulation.

【 授权许可】

Unknown