Transient Receptor Potential V Channels Are Essential for Glucose Sensing by Aldolase and AMPK

Fructose-1,6-bisphosphate (FBP) aldolase links sensing of declining glucose availability to AMPK activation via the lysosomal pathway. However, how aldolase transmits lack of occupancy by FBP to AMPK activation remains unclear. Here, we show that FBP-unoccupied aldolase interacts with and inhibits endoplasmic reticulum (ER)-localized transient receptor potential channel subfamily V, inhibiting calcium release in low glucose. The decrease of calcium at contact sites between ER and lysosome renders the inhibited TRPV accessible to bind the lysosomal v-ATPase that then recruits AXIN:LKB1 to activate AMPK independently of AMP. Genetic depletion of TRPVs blocks glucose starvation-induced AMPK activation in cells and liver of mice, and in nematodes, indicative of physical requirement of TRPVs. Pharmacological inhibition of TRPVs activates AMPK and elevates NAD(+) levels in aged muscles, rejuvenating the animals' running capacity. Our study elucidates that TRPVs relay the FBP-free status of aldolase to the reconfiguration of v-ATPase, leading to AMPK activation in low glucose

A numerical model of electrical characteristics for the monolayer graphene field effect transistors

A numerical model of carrier saturation velocity and drain current for the monolayer graphene field effect transistors (GFETs) is proposed by considering the exponential distribution of potential fluctuations in disordered graphene system. The carrier saturation velocity of GFET is investigated by the two-region model, and it is found to be affected not only by the carrier density, but also by the graphene disorder. The numerical solutions of the carrier density and carrier saturation velocity in the disordered GFETs yield clear and physical-based results. The simulated results of the drain current model show good consistency with the reported experimental data