{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T02:58:58Z","timestamp":1792897138549,"version":"4.5.0"},"reference-count":44,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province","award":["20210034"],"award-info":[{"award-number":["20210034"]}]},{"name":"Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province","award":["YDZJSX2021B001"],"award-info":[{"award-number":["YDZJSX2021B001"]}]},{"name":"Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province","award":["202203021211307"],"award-info":[{"award-number":["202203021211307"]}]},{"name":"Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province","award":["2023-007"],"award-info":[{"award-number":["2023-007"]}]},{"name":"Central Guidance on Local Science and Technology Development Fund of Shanxi Province","award":["20210034"],"award-info":[{"award-number":["20210034"]}]},{"name":"Central Guidance on Local Science and Technology Development Fund of Shanxi Province","award":["YDZJSX2021B001"],"award-info":[{"award-number":["YDZJSX2021B001"]}]},{"name":"Central Guidance on Local Science and Technology Development Fund of Shanxi Province","award":["202203021211307"],"award-info":[{"award-number":["202203021211307"]}]},{"name":"Central Guidance on Local Science and Technology Development Fund of Shanxi Province","award":["2023-007"],"award-info":[{"award-number":["2023-007"]}]},{"name":"Fundamental Research Program of Shanxi Province","award":["20210034"],"award-info":[{"award-number":["20210034"]}]},{"name":"Fundamental Research Program of Shanxi Province","award":["YDZJSX2021B001"],"award-info":[{"award-number":["YDZJSX2021B001"]}]},{"name":"Fundamental Research Program of Shanxi Province","award":["202203021211307"],"award-info":[{"award-number":["202203021211307"]}]},{"name":"Fundamental Research Program of Shanxi Province","award":["2023-007"],"award-info":[{"award-number":["2023-007"]}]},{"name":"Research Project Supported by Shanxi Scholarship Council of China","award":["20210034"],"award-info":[{"award-number":["20210034"]}]},{"name":"Research Project Supported by Shanxi Scholarship Council of China","award":["YDZJSX2021B001"],"award-info":[{"award-number":["YDZJSX2021B001"]}]},{"name":"Research Project Supported by Shanxi Scholarship Council of China","award":["202203021211307"],"award-info":[{"award-number":["202203021211307"]}]},{"name":"Research Project Supported by Shanxi Scholarship Council of China","award":["2023-007"],"award-info":[{"award-number":["2023-007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Fabry disease (FD) is an X-linked recessive inheritance lysosomal storage disorder caused by pathogenic mutations in the GLA gene leading to a deficiency of the enzyme alpha-galactosidase A (\u03b1-Gal A). Multiple organ systems are implicated in FD, most notably the kidney, heart, and central nervous system. In our previous study, we identified four GLA mutations from four independent Fabry disease families with kidney disease or neuropathic pain: c.119C&gt;A (p.P40H), c.280T&gt;C (C94R), c.680G&gt;C (p.R227P) and c.801+1G&gt;A (p.L268fsX3). To reveal the molecular mechanism underlying the predisposition to Fabry disease caused by GLA mutations, we analyzed the effects of these four GLA mutations on the protein structure of \u03b1-galactosidase A using bioinformatics methods. The results showed that these mutations have a significant impact on the internal dynamics and structures of GLA, and all these altered amino acids are close to the enzyme activity center and lead to significantly reduced enzyme activity. Furthermore, these mutations led to the accumulation of autophagosomes and impairment of autophagy in the cells, which may in turn negatively regulate autophagy by slightly increasing the phosphorylation of mTOR. Moreover, the overexpression of these GLA mutants promoted the expression of lysosome-associated membrane protein 2 (LAMP2), resulting in an increased number of lysosomes. Our study reveals the pathogenesis of these four GLA mutations in FD and provides a scientific foundation for accurate diagnosis and precise medical intervention for FD.<\/jats:p>","DOI":"10.3390\/cells13050437","type":"journal-article","created":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T11:19:24Z","timestamp":1709291964000},"page":"437","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["GLA Mutations Suppress Autophagy and Stimulate Lysosome Generation in Fabry Disease"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6137-6154","authenticated-orcid":false,"given":"Ping","family":"Li","sequence":"first","affiliation":[{"name":"Institutes of Biomedical Sciences, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education of China, The Key Laboratory of Medical Molecular Cell Biology of Shanxi Province, Shanxi University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqian","family":"Xi","sequence":"additional","affiliation":[{"name":"Institutes of Biomedical Sciences, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education of China, The Key Laboratory of Medical Molecular Cell Biology of Shanxi Province, Shanxi University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institutes of Biomedical Sciences, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education of China, The Key Laboratory of Medical Molecular Cell Biology of Shanxi Province, Shanxi University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdus","family":"Samad","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenli","family":"Lan","sequence":"additional","affiliation":[{"name":"Institutes of Biomedical Sciences, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education of China, The Key Laboratory of Medical Molecular Cell Biology of Shanxi Province, Shanxi University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Wu","sequence":"additional","affiliation":[{"name":"Institutes of Biomedical Sciences, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education of China, The Key Laboratory of Medical Molecular Cell Biology of Shanxi Province, Shanxi University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institutes of Biomedical Sciences, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education of China, The Key Laboratory of Medical Molecular Cell Biology of Shanxi Province, Shanxi University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangxin","family":"Chen","sequence":"additional","affiliation":[{"name":"Institutes of Biomedical Sciences, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education of China, The Key Laboratory of Medical Molecular Cell Biology of Shanxi Province, Shanxi University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changxin","family":"Wu","sequence":"additional","affiliation":[{"name":"Institutes of Biomedical Sciences, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education of China, The Key Laboratory of Medical Molecular Cell Biology of Shanxi Province, Shanxi University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuhong","family":"Xiong","sequence":"additional","affiliation":[{"name":"Institutes of Biomedical Sciences, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education of China, The Key Laboratory of Medical Molecular Cell Biology of Shanxi Province, Shanxi University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1159\/000060184","article-title":"Fabry disease (alpha-galactosidase A deficiency): Renal involvement and enzyme replacement therapy","volume":"136","author":"Desnick","year":"2001","journal-title":"Contrib. 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