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.

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Journal Article | Research Support, Non-U.S. Gov't

Authors

Klompmaker SH, Kohl K, Fasel N, Mayer A

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