Given here are simplified schematics of the NPC operating cycle. The NPC import process comprises two interlinked cycles. The first, shown in the upper panel, uses the energy released by the hydrolysis of one GTP molecule (catalyzed by RanGAP) to import one cargo molecule into the nucleus and relies on the higher concentration of RanGTP in the nucleus relative to the cytoplasm. The red line is the only nonequilibrium step of the import cycle that depends on the metabolic energy release in the form of GTP hydrolysis. The nucleocytoplasmic RanGTP/RanGDP gradient is maintained by the second cycle, shown in the lower panel, which relies on the high concentration of RanGEF in the nucleus due to its association with chromatin. To see this figure in color, go online.