摘要：Rods and cones use intracellular Ca2 to regulate many functions, including phototransduction and neurotransmission. The Mitochondrial Calcium Uniporter (MCU) complex is thought to be the primary pathway for Ca2 entry into mitochondria in eukaryotes. We investigate the hypothesis that mitochondrial Ca2 uptake via MCU influences phototransduction and energy metabolism in photoreceptors using a mcu-/- zebrafish and a rod photoreceptor-specific Mcu-/- mouse. Using genetically encoded Ca2 sensors to directly examine Ca2 uptake in zebrafish cone mitochondria, we found that loss of MCU reduces but does not eliminate mitochondrial Ca2 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 /Ca2 , 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 Ca2 uptake into photoreceptor mitochondria.
其他摘要：Abstract 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.
