Sensory neurons capture information from the environment and convert it into signals that can greatly impact the survival of an organism. These systems are thus under heavy selective pressure, including for the most efficient use of energy to support their sensitivity and efficiency1. In this regard, the vertebrate photoreceptor cells face a dual challenge. They not only need to preserve their membrane excitability via ion pumps by ATP hydrolysis2 but also maintain a highly membrane rich organelle, the outer segment, which is the primary site of phototransduction, creating a considerable biosynthetic demand. How photoreceptors manage carbon allocation to balance their catabolic and anabolic demands is poorly understood. One metabolic feature of the retina is its ability to convert the majority of its glucose into lactate3,4 even in the presence of oxygen. This phenomenon, aerobic glycolysis, is found in cancer and proliferating cells, and is thought to promote biomass buildup to sustain proliferation5,6. The purpose of aerobic glycolysis in the retina, its relevance to photoreceptor physiology, and its regulation, are not understood. Here, we show that rod photoreceptors rely on glycolysis for their outer segment (OS) biogenesis. Genetic perturbations targeting allostery or key regulatory nodes in the glycolytic pathway impacted the OS size. Fibroblast growth factor (FGF) signaling was found to regulate glycolysis, with antagonism of this pathway resulting in anabolic deficits. These data demonstrate the cell autonomous role of the glycolytic pathway in OS maintenance and provide evidence that aerobic glycolysis is part of a metabolic program that supports the biosynthetic needs of a normal neuronal cell type.

Vertebrate photoreceptors are among the most metabolically active cells, exhibiting a high rate of ATP consumption. This is coupled with a high anabolic demand, necessitated by the diurnal turnover of a specialized membrane-rich organelle, the outer segment, which is the primary site of phototransduction. How photoreceptors balance their catabolic and anabolic demands is poorly understood. Here, we show that rod photoreceptors in mice rely on glycolysis for their outer segment biogenesis. Genetic perturbations targeting allostery or key regulatory nodes in the glycolytic pathway impacted the size of the outer segments. Fibroblast growth factor signaling was found to regulate glycolysis, with antagonism of this pathway resulting in anabolic deficits. These data demonstrate the cell autonomous role of the glycolytic pathway in outer segment maintenance and provide evidence that aerobic glycolysis is part of a metabolic program that supports the biosynthetic needs of a normal neuronal cell type.DOI: http://dx.doi.org/10.7554/eLife.25946.001

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