Mitochondrial Calcium Uniporter (MCU) Deficiency Reveals an Alternate Path for Ca2+ Uptake in Photoreceptor Mitochondria

Rods and cones use intracellular Ca 2+ to regulate many functions, including phototransduction and neurotransmission. The Mitochondrial Calcium Uniporter (MCU) complex is thought to be the primary pathway for Ca 2+ entry into mitochondria in eukaryotes. We investigate the hypothesis that mitochondrial Ca 2+ uptake via MCU influences phototransduction and energy metabolism in photoreceptors using a mcu -/- zebrafish and a rod photoreceptor-specific Mcu -/- mouse. Using genetically encoded Ca 2+ sensors to directly examine Ca 2+ uptake in zebrafish cone mitochondria, we found that loss of MCU reduces but does not eliminate mitochondrial Ca 2+ uptake. Loss of MCU does not lead to photoreceptor degeneration, mildly affects mitochondrial metabolism, and does not alter physiological responses to light, even in the absence of the Na + /Ca 2+ , K + exchanger. Our results reveal that MCU is dispensable for vertebrate photoreceptor function, consistent with its low expression and the presence of an alternative pathway for Ca 2+ uptake into photoreceptor mitochondria.