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The mitochondrial calcium uniporter, which regulates aerobic metabolism by catalyzing mitochondrial Ca2+ influx, is arguably the most selective ion channel known. The uniporter is a multi-subunit complex comprising the protein MCU, which forms a tetrameric assembly and contains the ion pore, along with EMRE, MICU1 and MICU2 subunits. By combining structural studies of multiple complexes with functional studies, we have gained insight into the mechanisms for the channel’s Ca2+-dependent regulation and for its exquisite Ca2+ selectivity. The lecture will highlight recent work in which electrophysiological studies were used to probe ion selectivity mechanisms. Comparison with the structural information yields unexpected principals of selective Ca2+ conduction in the context of high ion throughput by the channel.
