{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T13:45:03Z","timestamp":1788961503019,"version":"build-2803163510"},"reference-count":65,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T00:00:00Z","timestamp":1751500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["EY014370"],"award-info":[{"award-number":["EY014370"]}]},{"name":"National Institutes of Health","award":["EY022230"],"award-info":[{"award-number":["EY022230"]}]},{"name":"National Institutes of Health","award":["EY0333516"],"award-info":[{"award-number":["EY0333516"]}]},{"name":"Thomas Foundation","award":["EY014370"],"award-info":[{"award-number":["EY014370"]}]},{"name":"Thomas Foundation","award":["EY022230"],"award-info":[{"award-number":["EY022230"]}]},{"name":"Thomas Foundation","award":["EY0333516"],"award-info":[{"award-number":["EY0333516"]}]},{"name":"Department of Ophthalmology, Wayne State University","award":["EY014370"],"award-info":[{"award-number":["EY014370"]}]},{"name":"Department of Ophthalmology, Wayne State University","award":["EY022230"],"award-info":[{"award-number":["EY022230"]}]},{"name":"Department of Ophthalmology, Wayne State University","award":["EY0333516"],"award-info":[{"award-number":["EY0333516"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mitochondria are dynamic in nature and depending on the energy demand they fuse and divide. This fusion-fission process is impaired in diabetic retinopathy and the promoter DNA of Mfn2, a fusion gene, is hypermethylated and its expression is downregulated. Long noncoding RNAs (RNAs with &gt;200 nucleotides that do not encode proteins) can regulate gene expression by interacting with DNA, RNA, and proteins. Several LncRNAs are aberrantly expressed in diabetes, and among them, MALAT1 is upregulated in the retina, altering the expression of the genes associated with inflammation. Our aim was to investigate MALAT1\u2019s role in mitochondrial dynamics in diabetic retinopathy. Using MALAT1-siRNA-transfected human retinal endothelial cells (HRECs) and human retinal Muller cells (RMCs) incubated in 20 mM D-glucose, Mfn2 expression and activity and its promoter DNA methylation were quantified. Mitochondrial integrity was evaluated by analyzing their fragmentation, ultrastructure, membrane potential, and oxygen consumption rate. Compared to normal glucose, high glucose upregulated MALAT1 expression and downregulated Mfn2 expression and activity in both HRECs and RMCs. MALAT1-siRNA ameliorated the glucose-induced increase in Mfn2 promoter DNA hypermethylation and its activity. MALAT1-siRNA also protected against mitochondrial fragmentation, structural damage, and reductions in the oxygen consumption rate. In conclusion, the upregulation of MALAT1 in diabetes facilitates Mfn2 promoter DNA hypermethylation in retinal vascular and nonvascular cells, leading to its suppression and the accumulation of the fragmented\/damaged mitochondria. Thus, the regulation of MALAT1 has the potential to protect mitochondria and provide a possible new target to inhibit\/prevent the blinding disease in diabetic patients.<\/jats:p>","DOI":"10.3390\/ijms26136429","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T09:57:39Z","timestamp":1751536659000},"page":"6429","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Mitochondrial Fragmentation and Long Noncoding RNA MALAT1 in Diabetic Retinopathy"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3309-4942","authenticated-orcid":false,"given":"Renu A.","family":"Kowluru","sequence":"first","affiliation":[{"name":"Ophthalmology, Visual and Anatomical Sciences, Kresge Eye Institute, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay","family":"Kumar","sequence":"additional","affiliation":[{"name":"Ophthalmology, Visual and Anatomical Sciences, Kresge Eye Institute, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/S0002-9394(03)00219-8","article-title":"Perspectives on diabetic retinopathy","volume":"136","author":"Aiello","year":"2003","journal-title":"Am. 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