期刊
EBIOMEDICINE
卷 16, 期 -, 页码 292-301出版社
ELSEVIER
DOI: 10.1016/j.ebiom.2017.01.004
关键词
Glutaminolysis; Energy metabolism; Corneal endothelium; SLC4A11 ammonia transporter; Congenital hereditary endothelial dystrophy (CHED); Fuchs' endothelial corneal dystrophy (FECD)
资金
- NIH [5R01EY008834, 5P30EY019008, 5R00GM101341-05, 1R35GM119557-01]
- National Academy of Sciences
- Eye Bank Association of America Richard Lindstrom Research Grants
- American Optometric Foundation William C. Ezell Fellowship
Corneal endothelium (CE) is among the most metabolically active tissues in the body. This elevated metabolic rate helps the CE maintain corneal transparency by its ion and fluid transport properties, which when disrupted, leads to visual impairment. Here we demonstrate that glutamine catabolism(glutaminolysis) through TCA cycle generates a large fraction of the ATP needed to maintain CE function, and this glutaminolysis is severely disrupted in cells deficient in NH3:H+ cotransporter Solute Carrier Family 4 Member 11 (SLC4A11). Considering SLC4A11 mutations leads to corneal endothelial dystrophy and sensorineural deafness, our results indicate that SLC4A11-associated developmental and degenerative disorders result from altered glutamine catabolism. Overall, our results describe an important metabolic mechanism that provides CE cells with the energy required to maintain high level transport activity, reveal a direct link between glutamine metabolism and developmental and degenerative neuronal diseases, and suggest an approach for protecting the CE during ophthalmic surgeries. (C) 2017 The Authors. Published by Elsevier B.V.
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