{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:14:14Z","timestamp":1788480854849,"version":"build-2803163510"},"reference-count":101,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T00:00:00Z","timestamp":1680739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Higher Education Malaysia via the Fundamental Research Grant Scheme","award":["FRGS\/1\/2022\/SKK06\/UM\/02\/5"],"award-info":[{"award-number":["FRGS\/1\/2022\/SKK06\/UM\/02\/5"]}]},{"name":"Ministry of Higher Education Malaysia via the Fundamental Research Grant Scheme","award":["FRGS\/1\/2016\/SKK06\/UM\/02\/8"],"award-info":[{"award-number":["FRGS\/1\/2016\/SKK06\/UM\/02\/8"]}]},{"name":"Ministry of Higher Education Malaysia via the Fundamental Research Grant Scheme","award":["PV036-2020"],"award-info":[{"award-number":["PV036-2020"]}]},{"name":"Ministry of Higher Education Malaysia via the Fundamental Research Grant Scheme","award":["GPF003C-2019"],"award-info":[{"award-number":["GPF003C-2019"]}]},{"name":"Private Funding","award":["FRGS\/1\/2022\/SKK06\/UM\/02\/5"],"award-info":[{"award-number":["FRGS\/1\/2022\/SKK06\/UM\/02\/5"]}]},{"name":"Private Funding","award":["FRGS\/1\/2016\/SKK06\/UM\/02\/8"],"award-info":[{"award-number":["FRGS\/1\/2016\/SKK06\/UM\/02\/8"]}]},{"name":"Private Funding","award":["PV036-2020"],"award-info":[{"award-number":["PV036-2020"]}]},{"name":"Private Funding","award":["GPF003C-2019"],"award-info":[{"award-number":["GPF003C-2019"]}]},{"name":"RU Geran\u2013Fakulti Program via University of Malaya Faculty of Medicine Research Grant","award":["FRGS\/1\/2022\/SKK06\/UM\/02\/5"],"award-info":[{"award-number":["FRGS\/1\/2022\/SKK06\/UM\/02\/5"]}]},{"name":"RU Geran\u2013Fakulti Program via University of Malaya Faculty of Medicine Research Grant","award":["FRGS\/1\/2016\/SKK06\/UM\/02\/8"],"award-info":[{"award-number":["FRGS\/1\/2016\/SKK06\/UM\/02\/8"]}]},{"name":"RU Geran\u2013Fakulti Program via University of Malaya Faculty of Medicine Research Grant","award":["PV036-2020"],"award-info":[{"award-number":["PV036-2020"]}]},{"name":"RU Geran\u2013Fakulti Program via University of Malaya Faculty of Medicine Research Grant","award":["GPF003C-2019"],"award-info":[{"award-number":["GPF003C-2019"]}]},{"name":"Universiti Malaya Page Charge Fund","award":["FRGS\/1\/2022\/SKK06\/UM\/02\/5"],"award-info":[{"award-number":["FRGS\/1\/2022\/SKK06\/UM\/02\/5"]}]},{"name":"Universiti Malaya Page Charge Fund","award":["FRGS\/1\/2016\/SKK06\/UM\/02\/8"],"award-info":[{"award-number":["FRGS\/1\/2016\/SKK06\/UM\/02\/8"]}]},{"name":"Universiti Malaya Page Charge Fund","award":["PV036-2020"],"award-info":[{"award-number":["PV036-2020"]}]},{"name":"Universiti Malaya Page Charge Fund","award":["GPF003C-2019"],"award-info":[{"award-number":["GPF003C-2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Adenosine is a nucleoside that is widely distributed in the central nervous system and acts as a central excitatory and inhibitory neurotransmitter in the brain. The protective role of adenosine in different pathological conditions and neurodegenerative diseases is mainly mediated by adenosine receptors. However, its potential role in mitigating the deleterious effects of oxidative stress in Friedreich\u2019s ataxia (FRDA) remains poorly understood. We aimed to investigate the protective effects of adenosine against mitochondrial dysfunction and impaired mitochondrial biogenesis in L-buthionine sulfoximine (BSO)-induced oxidative stress in dermal fibroblasts derived from an FRDA patient. The FRDA fibroblasts were pre-treated with adenosine for 2 h, followed by 12.50 mM BSO to induce oxidative stress. Cells in medium without any treatments or pre-treated with 5 \u00b5M idebenone served as the negative and positive controls, respectively. Cell viability, mitochondrial membrane potential (MMP), aconitase activity, adenosine triphosphate (ATP) level, mitochondrial biogenesis, and associated gene expressions were assessed. We observed disruption of mitochondrial function and biogenesis and alteration in gene expression patterns in BSO-treated FRDA fibroblasts. Pre-treatment with adenosine ranging from 0\u2013600 \u00b5M restored MMP, promoted ATP production and mitochondrial biogenesis, and modulated the expression of key metabolic genes, namely nuclear respiratory factor 1 (NRF1), transcription factor A, mitochondrial (TFAM), and NFE2-like bZIP transcription factor 2 (NFE2L2). Our study demonstrated that adenosine targeted mitochondrial defects in FRDA, contributing to improved mitochondrial function and biogenesis, leading to cellular iron homeostasis. Therefore, we suggest a possible therapeutic role for adenosine in FRDA.<\/jats:p>","DOI":"10.3390\/biology12040559","type":"journal-article","created":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T08:41:52Z","timestamp":1680770512000},"page":"559","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Adenosine Improves Mitochondrial Function and Biogenesis in Friedreich\u2019s Ataxia Fibroblasts Following L-Buthionine Sulfoximine-Induced Oxidative Stress"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5402-6869","authenticated-orcid":false,"given":"Sze Yuen","family":"Lew","sequence":"first","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nur Shahirah","family":"Mohd Hisam","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Weng Lok","family":"Phang","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syarifah Nur","family":"Syed Abdul Rahman","sequence":"additional","affiliation":[{"name":"Department of Oral and Craniofacial Sciences, Faculty of Dentistry, Universiti Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7893-9929","authenticated-orcid":false,"given":"Rozaida Yuen Ying","family":"Poh","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siew Huah","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, Universiti Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4163-2234","authenticated-orcid":false,"given":"Mohd Amir","family":"Kamaruzzaman","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latiff, Cheras, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sze Chun","family":"Chau","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1366-1284","authenticated-orcid":false,"given":"Ka Chun","family":"Tsui","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6692-6285","authenticated-orcid":false,"given":"Lee Wei","family":"Lim","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8292-4498","authenticated-orcid":false,"given":"Kah Hui","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia"},{"name":"School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1056\/NEJM199610173351601","article-title":"Clinical and genetic abnormalities in patients with Friedreich\u2019s ataxia","volume":"335","author":"Cossee","year":"1996","journal-title":"N. 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