Mitochondrial Calcium Uniporter (MCU) deficiency reveals an alternate path for Ca(2+) 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.