Fig. 1. Copper homeostasis in macrophages.
A. In resting macrophages CTR1 imports Cu(I) which is bound by the chaperone ATOX1. ATP7A is localized to the Golgi Network to deliver Cu to copper-requiring proteins. B. Under copper-stress ATP7A is trafficked to the membrane to export excess copper, but its transcription and translation are not increased. C. Initially upon phagocytosis into macrophages, M. tuberculosis suppresses phagolysosome formation. D. Once infected macrophages are activated with IFN-γ, phagolysosome fusion proceeds, the pH of the M. tuberculosis containing vacuole is reduced to pH4.5, CTR1 and ATP7A expression is increased and ATP7A is trafficked to the phagolysosome.