MCU Interacts with Mirol to Modulate Mitochondrial Functions In Neurons

Mitochondrial Ca2+ uptake is gated by the mitochondrial calcium uniplex, which is comprised of mitochondrial calcium uniporter (MCU),the Ca2+ pore-forming subunit of the complex, and its regulators. Ca2+ ' influx through MCU affects both mitochondrial function and movement in neurons, but its direct role in mitochondrial movement has not been explored. In this report, we show a link between MCU and Mirol, a membrane protein known to regulate mitochondrial movement. We find that MCU interacts with Mirol through MCU's N-terminal domain, previously thought to be the mitochondrial targeting sequence. Our results showthat the N-terminus of MCU has a transmembrane domain that traverses the outer mitochondrial membrane, which is dispensable for MCU localization into mitochondria. However, this domain is required for Mirol interaction and is critical for Mirol directed movement. Together, our findings reveal Mirol as a new component of the MCU complex, and that MCU is an important regulator of mitochondrial transport.