A highly conserved zebrafish IMPDH retinal isoform produces the majority of guanine and forms dynamic protein filaments in photoreceptor cells.

Inosine monophosphate dehydrogenase (IMPDH) is a key regulatory enzyme in the de novo synthesis of the purine base guanine. Dominant mutations in human IMPDH1 cause photoreceptor degeneration for reasons that are unknown. Here, we sought to provide some foundational information on Impdh1a in the zebrafish retina.

Daily mitochondrial dynamics in cone photoreceptors.

Cone photoreceptors in the retina are exposed to intense daylight and have higher energy demands in darkness. Cones produce energy using a large cluster of mitochondria. Mitochondria are susceptible to oxidative damage, and healthy mitochondrial populations are maintained by regular turnover.

Mitochondrial Calcium Uniporter (MCU) deficiency reveals an alternate path for Ca uptake in photoreceptor mitochondria.

Rods and cones use intracellular Ca to regulate many functions, including phototransduction and neurotransmission. The Mitochondrial Calcium Uniporter (MCU) complex is thought to be the primary pathway for Ca entry into mitochondria in eukaryotes. We investigate the hypothesis that mitochondrial Ca uptake via MCU influences phototransduction and energy metabolism in photoreceptors using a mcu zebrafish and a rod photoreceptor-specific Mcu mouse.

Increasing Ca in photoreceptor mitochondria alters metabolites, accelerates photoresponse recovery, and reveals adaptations to mitochondrial stress.

Photoreceptors are specialized neurons that rely on Ca to regulate phototransduction and neurotransmission. Photoreceptor dysfunction and degeneration occur when intracellular Ca homeostasis is disrupted. Ca homeostasis is maintained partly by mitochondrial Ca uptake through the mitochondrial Ca uniporter (MCU), which can influence cytosolic Ca signals, stimulate energy production, and trigger apoptosis.