Department of Ophthalmology; Gene Therapy Center; Division of Pulmonary Medicine, Department of Pediatrics; UMass Metabolic Network
Biochemical Phenomena, Metabolism, and Nutrition | Cellular and Molecular Physiology | Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Enzymes and Coenzymes | Eye Diseases
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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Copyright 2018 The Author(s). 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, Lolita; Ma, Shan; Cipi, Joris; Cheng, Shun-Yun; Zieger, Marina; Hay, Nissim; and Punzo, Claudio, "Aerobic Glycolysis Is Essential for Normal Rod Function and Controls Secondary Cone Death in Retinitis Pigmentosa" (2018). University of Massachusetts Medical School Faculty Publications. 1586.
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Biochemical Phenomena, Metabolism, and Nutrition Commons, Cellular and Molecular Physiology Commons, Congenital, Hereditary, and Neonatal Diseases and Abnormalities Commons, Enzymes and Coenzymes Commons, Eye Diseases Commons