{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T13:00:59Z","timestamp":1788267659800,"version":"build-2803163510"},"reference-count":33,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T00:00:00Z","timestamp":1635379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["2019R1A2C1010634, NRF-2017M3C7A1048092, 21-BR-02-19"],"award-info":[{"award-number":["2019R1A2C1010634, NRF-2017M3C7A1048092, 21-BR-02-19"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Iron overload in the brain, defined as excess stores of iron, is known to be associated with neurological disorders. In neurodegeneration accompanied by brain iron accumulation, we reported a specific point mutation, c.974-1G&gt;A in WD Repeat Domain 45 (WDR45), showing iron accumulation in the brain, and autophagy defects in the fibroblasts. In this study, we investigated whether fibroblasts with mutated WDR45 accumulated iron, and other effects on cellular organelles. We first identified the main location of iron accumulation in the mutant fibroblasts and then investigated the effects of this accumulation on cellular organelles, including lipid droplets, mitochondria and lysosomes. Ultrastructure analysis using transmission electron microscopy (TEM) and confocal microscopy showed structural changes in the organelles. Increased numbers of lipid droplets, fragmented mitochondria and increased numbers of lysosomal vesicles with functional disorder due to WDR45 deficiency were observed. Based on correlative light and electron microscopy (CLEM) findings, most of the iron accumulation was noted in the lysosomal vesicles. These changes were associated with defects in autophagy and defective protein and organelle turnover. Gene expression profiling analysis also showed remarkable changes in lipid metabolism, mitochondrial function, and autophagy-related genes. These data suggested that functional and structural changes resulted in impaired lipid metabolism, mitochondrial disorder, and unbalanced autophagy fluxes, caused by iron overload.<\/jats:p>","DOI":"10.3390\/ijms222111650","type":"journal-article","created":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T23:51:36Z","timestamp":1635465096000},"page":"11650","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Iron Accumulation and Changes in Cellular Organelles in WDR45 Mutant Fibroblasts"],"prefix":"10.3390","volume":"22","author":[{"given":"Hye Eun","family":"Lee","sequence":"first","affiliation":[{"name":"Neural Circuit Research Group, Korea Brain Research Institute, Daegu 41068, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3288-3288","authenticated-orcid":false,"given":"Min Kyo","family":"Jung","sequence":"additional","affiliation":[{"name":"Neural Circuit Research Group, Korea Brain Research Institute, Daegu 41068, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seul Gi","family":"Noh","sequence":"additional","affiliation":[{"name":"Neural Circuit Research Group, Korea Brain Research Institute, Daegu 41068, Korea"},{"name":"Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology, Daegu 42988, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Bin","family":"Choi","sequence":"additional","affiliation":[{"name":"Neurovascular Unit Research Group, Korea Brain Research Institute, Daegu 41068, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se hyun","family":"Chae","sequence":"additional","affiliation":[{"name":"Neurovascular Unit Research Group, Korea Brain Research Institute, Daegu 41068, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4274-7415","authenticated-orcid":false,"given":"Jae Hyeok","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Korea"},{"name":"Medical Research Institute, Pusan National University School of Medicine, Yangsan 50612, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Young","family":"Mun","sequence":"additional","affiliation":[{"name":"Neural Circuit Research Group, Korea Brain Research Institute, Daegu 41068, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,28]]},"reference":[{"key":"ref_1","unstructured":"Gregory, A., and Hayflick, S. 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