{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:11:35Z","timestamp":1790946695234,"version":"4.1.0"},"reference-count":81,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Gaucher disease (GD) is an autosomal recessive metabolic disorder caused by pathogenic variants in the GBA1 gene, which encodes the lysosomal hydrolase \u03b2-glucocerebrosidase (GCase). The pathogenic defects result in a misfolded protein, which can trigger endoplasmic reticulum stress and an unfolded protein response within the affected cells. The reduced enzyme activity leads to accumulation of its substrates, glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph), within lysosomes or macrophages and with prominent disease manifestations in reticuloendothelial tissues such as liver, spleen and bone marrow. GCase defects alter both the mitochondria and the lysosome. In the lysosome, reduced GCase activity leads to glycosphingolipid build-up, disrupting lysosomal function and autophagy, thereby activating \u03b1-synuclein accumulation. GCase can also be imported into the mitochondria, where it fosters the integrity and function of mitochondrial respiratory chain (MRC) complex I. Thus, the reduced GCase activity impairs the normal mitochondrial function and increases oxidative stress in this organelle, which may contribute to cell death. However, further studies are required to confirm this mechanism of MRC dysfunction. In this review we have systematically evaluated the evidence for oxidative stress in individuals affected by GD, as well as the currently available therapies and adjunctive therapies. Therapies targeting oxidative stress may prove useful as adjuvant treatments for GD.<\/jats:p>","DOI":"10.3390\/genes16111269","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T11:47:19Z","timestamp":1761652039000},"page":"1269","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Secondary Mitochondrial Dysfunction in Gaucher Disease Type I, II and III\u2014Review of the Experimental and Clinical Evidence"],"prefix":"10.3390","volume":"16","author":[{"given":"Mollie","family":"Dewsbury","sequence":"first","affiliation":[{"name":"School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"Purcell","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4531-9173","authenticated-orcid":false,"given":"Derralynn","family":"Hughes","sequence":"additional","affiliation":[{"name":"Royal Free London NHS Foundation Trust, University College London, Pond Street, London NW3 2QG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimee","family":"Donald","sequence":"additional","affiliation":[{"name":"Manchester Foundation Trust, Oxford Road, Manchester M13 9WL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain P.","family":"Hargreaves","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK"},{"name":"Neurometabolic Unit, National Hospital, London WC1N 3BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0148-6332","authenticated-orcid":false,"given":"Karolina M.","family":"Stepien","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK"},{"name":"Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, UK"},{"name":"Division of Cardiovascular Sciences, University of Manchester, Oxford Road, Manchester M13 9WL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"key":"ref_1","unstructured":"Mehta, A., Beck, M., and Sunder-Plassmann, G. 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