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Intriguingly, these truncated GCLC fragments compete with full-length GCLC in forming a heterocomplex with the modifier subunit (GCLM) but exhibit markedly reduced enzymatic activity. Crucially, using an aspartate-to-glutamate mutation knock-in (D499E-KI) mouse model that blocks GCLC truncation, we observed a notable delay in ARC formation compared to WT mice: Nearly 50% of D499E-KI mice remained cataract-free versus ~20% of the WT mice at their age of 20 months. Our findings concerning age-related GCLC truncation might be the key to understanding the profound reduction in lens GSH with age. By halting GCLC truncation, we can rejuvenate lens GSH levels and considerably postpone cataract onset.<\/jats:p>","DOI":"10.1126\/sciadv.adl1088","type":"journal-article","created":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T13:58:41Z","timestamp":1714139921000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":20,"title":["Prevention of age-related truncation of \u03b3-glutamylcysteine ligase catalytic subunit (GCLC) delays cataract formation"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6530-8968","authenticated-orcid":true,"given":"Zongbo","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, GA 30912, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6743-6222","authenticated-orcid":true,"given":"Caili","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, GA 30912, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazi Rafsan","family":"Radeen","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, GA 30912, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2542-1501","authenticated-orcid":true,"given":"Ramkumar","family":"Srinivasagan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9490-5588","authenticated-orcid":true,"given":"Jian-Kang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, GA 30912, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8200-108X","authenticated-orcid":true,"given":"Shruti","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Medical College of Georgia at Augusta University, Augusta, GA 30912, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2728-5849","authenticated-orcid":true,"given":"Meghan E.","family":"McGee-Lawrence","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, GA 30912, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark W.","family":"Hamrick","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, GA 30912, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4894-3142","authenticated-orcid":true,"given":"Vincent M.","family":"Monnier","sequence":"additional","affiliation":[{"name":"Department of Pathology and Biochemistry, Case Western Reserve University, Cleveland, OH 44106, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6477-4465","authenticated-orcid":true,"given":"Xingjun","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, GA 30912, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01839-6"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(20)30489-7"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30544-5"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2020.100905"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells11132001"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0886-3350(97)80050-8"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0886-3350(13)80644-X"},{"key":"e_1_3_2_9_2","first-page":"249","volume":"79","author":"Brian G.","year":"2001","unstructured":"G. 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