Phytocannabinoid-dependent mTORC1 regulation is dependent upon inositol polyphosphate multikinase activity.

Background And Purpose: Cannabidiol (CBD) has been shown to differentially regulate the mechanistic target of rapamycin complex 1 (mTORC1) in preclinical models of disease, where it reduces activity in models of epilepsies and cancer and increases it in models of multiple sclerosis (MS) and psychosis. Here, we investigate the effects of phytocannabinoids on mTORC1 and define a molecular mechanism.

Experimental Approach: A novel mechanism for phytocannabinoids was identified using the tractable model system, Dictyostelium discoideum.

A mitochondrial fluorescent tagging vector that does not affect respiratory function.

Visualizing mitochondria in living cells using fluorescent dyes is often problematic due to variability in staining, metabolism of the dyes, and unknown potential effects of the dyes on mitochondrial function. We show that fluorescent labelling of mitochondria, using an N-terminal mitochondrial localization sequence derived from the protein GcvH1 (glycine cleavage system H1) attached to a red fluorescent protein enables clear mitochondrial imaging. We also show that this labelling has no effect upon mitochondria load or respiratory function.