UMMS Affiliation
Department of Ophthalmology; Gene Therapy Center; Department of Pediatrics, Division of Pulmonary Medicine; UMass Metabolic Network
Publication Date
2018-05-29
Document Type
Article
Disciplines
Cellular and Molecular Physiology | Eye Diseases | Ophthalmology
Abstract
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.
Keywords
Aerobic glycolysis, cones, hexokinase-2, metabolic coupling, oxidative phosphorylation, retinitis pigmentosa, rod metabolism, rods
Rights and Permissions
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
10.1016/j.celrep.2018.04.111
Source
Cell Rep. 2018 May 29;23(9):2629-2642. doi: 10.1016/j.celrep.2018.04.111. Link to article on publisher's site
Journal/Book/Conference Title
Cell reports
Related Resources
PubMed ID
29847794
Repository Citation
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). Open Access Articles. 3490.
https://escholarship.umassmed.edu/oapubs/3490
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.