Department of Ophthalmology; Gene Therapy Center; Department of Pediatrics, Division of Pulmonary Medicine; UMass Metabolic Network
Cellular and Molecular Physiology | Eye Diseases | Ophthalmology
Aerobic glycolysis accounts for approximately 80%-90% of glucose used by adult photoreceptors (PRs); yet, the importance of aerobic glycolysis for PR function or survival remains unclear. Here, we further established the role of aerobic glycolysis in murine rod and cone PRs. We show that loss of hexokinase-2 (HK2), a key aerobic glycolysis enzyme, does not affect PR survival or structure but is required for normal rod function. Rods with HK2 loss increase their mitochondrial number, suggesting an adaptation to the inhibition of aerobic glycolysis. In contrast, cones adapt without increased mitochondrial number but require HK2 to adapt to metabolic stress conditions such as those encountered in retinitis pigmentosa, where the loss of rods causes a nutrient shortage in cones. The data support a model where aerobic glycolysis in PRs is not a necessity but rather a metabolic choice that maximizes PR function and adaptability to nutrient stress conditions.
Aerobic glycolysis, cones, hexokinase-2, metabolic coupling, oxidative phosphorylation, retinitis pigmentosa, rod metabolism, rods
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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
DOI of Published Version
Cell Rep. 2018 May 29;23(9):2629-2642. doi: 10.1016/j.celrep.2018.04.111. Link to article on publisher's site
Petit L, Ma S, Cipi J, Cheng S, Zieger M, Hay N, Punzo C. (2018). Aerobic Glycolysis Is Essential for Normal Rod Function and Controls Secondary Cone Death in Retinitis Pigmentosa. Open Access Publications by UMass Chan Authors. https://doi.org/10.1016/j.celrep.2018.04.111. Retrieved from https://escholarship.umassmed.edu/oapubs/3490
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.