{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T13:54:17Z","timestamp":1776779657468,"version":"3.51.2"},"reference-count":90,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,20]],"date-time":"2023-10-20T00:00:00Z","timestamp":1697760000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Knights Templar Eye Foundation Career-Starter Research Grant (MY)","award":["EY08098"],"award-info":[{"award-number":["EY08098"]}]},{"name":"University of Pittsburgh start-up funds (DS)","award":["EY08098"],"award-info":[{"award-number":["EY08098"]}]},{"name":"Jennifer Salvitti Davis, M.D. Chair Professorship in Ophthalmology (DS)","award":["EY08098"],"award-info":[{"award-number":["EY08098"]}]},{"name":"National Eye Institute, NIH","award":["EY08098"],"award-info":[{"award-number":["EY08098"]}]},{"name":"Research to Prevent Blindness Inc., NY","award":["EY08098"],"award-info":[{"award-number":["EY08098"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Mitochondrial dysfunction in astrocytes has been implicated in the development of various neurological disorders. Mitophagy, mitochondrial autophagy, is required for proper mitochondrial function by preventing the accumulation of damaged mitochondria. The importance of mitophagy, specifically in the astrocytes of the optic nerve (ON), has been little studied. We introduce an animal model in which two separate mutations act synergistically to produce severe ON degeneration. The first mutation is in Cryba1, which encodes \u03b2A3\/A1-crystallin, a lens protein also expressed in astrocytes, where it regulates lysosomal pH. The second mutation is in Bckdk, which encodes branched-chain ketoacid dehydrogenase kinase, which is ubiquitously expressed in the mitochondrial matrix and involved in the catabolism of the branched-chain amino acids. BCKDK is essential for mitochondrial function and the amelioration of oxidative stress. Neither of the mutations in isolation has a significant effect on the ON, but animals homozygous for both mutations (DM) exhibit very serious ON degeneration. ON astrocytes from these double-mutant (DM) animals have lysosomal defects, including impaired mitophagy, and dysfunctional mitochondria. Urolithin A can rescue the mitophagy impairment in DM astrocytes and reduce ON degeneration. These data demonstrate that efficient mitophagy in astrocytes is required for ON health and functional integrity.<\/jats:p>","DOI":"10.3390\/cells12202496","type":"journal-article","created":{"date-parts":[[2023,10,20]],"date-time":"2023-10-20T11:53:56Z","timestamp":1697802836000},"page":"2496","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Mitophagy in Astrocytes Is Required for the Health of Optic Nerve"],"prefix":"10.3390","volume":"12","author":[{"given":"Meysam","family":"Yazdankhah","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sayan","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3757-779X","authenticated-orcid":false,"given":"Haitao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stacey","family":"Hose","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"J. Samuel","family":"Zigler","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Wilmer Eye Institute, The Johns Hopkins School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debasish","family":"Sinha","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"},{"name":"Department of Ophthalmology, The Wilmer Eye Institute, The Johns Hopkins School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"624983","DOI":"10.3389\/fneur.2021.624983","article-title":"Glial Cells in Glaucoma: Friends, Foes, and Potential Therapeutic Targets","volume":"12","author":"Freude","year":"2021","journal-title":"Front. 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