Mitochondrial Ca2+ influences photoresponse recovery, metabolism, and mitochondrial localization in cone photoreceptors

Mitochondrial Ca 2+ regulates key cellular processes including cytosolic Ca 2+ signals, energy production, and susceptibility to apoptosis. Photoreceptors are specialized neurons that have extraordinarily high energy demands and rely on cytosolic Ca 2+ signals for light adaptation and neurotransmission. Here we show that unlike other neurons zebrafish cone photoreceptors express low levels of the mitochondrial Ca 2+ uniporter (MCU), the channel that allows mitochondrial Ca 2+ entry. To determine why MCU expression is kept low, we overexpressed MCU specifically in cones. This increases mitochondrial [Ca 2+ ], causes faster cytosolic Ca 2+ clearance, and accelerates photoresponse recovery. Moreover, flux through the citric acid cycle increases despite dramatic changes in mitochondrial ultrastructure and localization. Remarkably, cones survive this ongoing stress until late adulthood. Our findings demonstrate the importance of tuning mitochondrial Ca 2+ influx to modulate physiological and metabolic processes and reveal a novel directed movement of abnormal mitochondria in photoreceptors.