{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:49:24Z","timestamp":1790272164256,"version":"4.1.0"},"reference-count":19,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T00:00:00Z","timestamp":1615248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2017\/25\/B\/NZ2\/00414"],"award-info":[{"award-number":["2017\/25\/B\/NZ2\/00414"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mucopolysaccharidoses (MPS) are inherited metabolic diseases characterized by accumulation of incompletely degraded glycosaminoglycans (GAGs) in lysosomes. Although primary causes of these diseases are mutations in genes coding for enzymes involved in lysosomal GAG degradation, it was demonstrated that storage of these complex carbohydrates provokes a cascade of secondary and tertiary changes affecting cellular functions. Potentially, this might lead to appearance of cellular disorders which could not be corrected even if the primary cause of the disease is removed. In this work, we studied changes in cellular organelles in MPS fibroblasts relative to control cells. All 11 types and subtypes of MPS were included into this study to obtain a complex picture of changes in organelles in this group of diseases. Two experimental approaches were employed, transcriptomic analyses and electron microscopic assessment of morphology of organelles. We analyzed levels of transcripts of genes grouped into two terms included into the QuickGO database, \u2018Cellular component organization\u2019 (GO:0016043) and \u2018Cellular anatomical entity\u2019 (GO:0110165), to find that number of transcripts with significantly changed levels in MPS fibroblasts vs. controls ranged from 109 to 322 (depending on MPS type) in GO:0016043, and from 70 to 208 in GO:0110165. This dysregulation of expression of genes crucial for proper structures and functions of various organelles was accompanied by severe changes in morphologies of lysosomes, nuclei, mitochondria, Golgi apparatus, and endoplasmic reticulum. Interestingly, some observed changes occurred in all\/most MPS types while others were specific to particular disease types\/subtypes. We suggest that severe changes in organelles in MPS cells might arise from dysregulation of expression of a battery of genes involved in organelles\u2019 structures and functions. Intriguingly, normalization of GAG levels by using recombinant human enzymes specific to different MPS types corrected morphologies of some, but not all, organelles, while it failed to improve regulation of expression of selected genes. These results might suggest reasons for inability of enzyme replacement therapy to correct all MPS symptoms, particularly if initiated at advanced stages of the disease.<\/jats:p>","DOI":"10.3390\/ijms22052766","type":"journal-article","created":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T12:08:01Z","timestamp":1615291681000},"page":"2766","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Gene Expression-Related Changes in Morphologies of Organelles and Cellular Component Organization in Mucopolysaccharidoses"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0820-7204","authenticated-orcid":false,"given":"Lidia","family":"Gaffke","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3634-6567","authenticated-orcid":false,"given":"Karolina","family":"Pierzynowska","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estera","family":"Rintz","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzanna","family":"Cyske","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1670-6636","authenticated-orcid":false,"given":"Izabela","family":"Giecewicz","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4042-7466","authenticated-orcid":false,"given":"Grzegorz","family":"W\u0119grzyn","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,9]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2020, December 29). 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