Abstract
Cells acquire free metals through plasma membrane transporters. But, in natural settings, sequestering agents often render metals inaccessible to transporters, limiting metal bioavailability. Here we identify a pathway for metal acquisition, allowing cells to cope with this situation. Under limited bioavailability of Mg2+, yeast cells upregulate fluid-phase endocytosis and transfer solutes from the environment into their vacuole, an acidocalcisome-like compartment loaded with highly concentrated polyphosphate. We propose that this anionic inorganic polymer, which is an avid chelator of Mg2+, serves as an immobilized cation filter that accumulates Mg2+ inside these organelles. It thus allows the vacuolar exporter Mnr2 to efficiently transfer Mg2+ into the cytosol. Leishmania parasites also employ acidocalcisomal polyphosphate to multiply in their Mg2+-limited habitat, the phagolysosomes of inflammatory macrophages. This suggests that the pathway for metal uptake via endocytosis, acidocalcisomal polyphosphates and export into the cytosol, which we term EAPEC, is conserved.