Abstract
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.
Highlights
Sensory neurons capture information from the environment and convert it into signals that can greatly impact the survival of an organism
Lactate is produced by reduction of pyruvate, a reaction catalyzed by lactate dehydrogenase (LDH) (Figure 1—figure supplement 2A)
Inhibiting lactate synthesis resulted in a greater fraction of the ATP pool that was sensitive to mitochondrial function
Summary
Sensory neurons capture information from the environment and convert it into signals that can greatly impact the survival of an organism These systems are under heavy selective pressure, including for the most efficient use of energy to support their sensitivity and efficiency (Niven and Laughlin, 2008). The primary photoreceptor cells face a dual challenge They need to preserve their membrane excitability via ion pumps by ATP hydrolysis (Okawa et al, 2008) and maintain elaborate membranous organelles (rhabdomeres in invertebrates and outer segments in vertebrates) that maximize light capture. The maintenance of such structures requires considerable metabolic resources. Photoreceptors must balance the use of their intracellular carbon pool between oxidative catabolism, to generate the required ATP, and anabolism, to continually renew the OS
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