{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:57:36Z","timestamp":1760144256730,"version":"build-2065373602"},"reference-count":55,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,3,30]],"date-time":"2024-03-30T00:00:00Z","timestamp":1711756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["MOST 108-2321-B-002-060-MY2","110-CCH-IRP-097","111-CCH-IRP-065"],"award-info":[{"award-number":["MOST 108-2321-B-002-060-MY2","110-CCH-IRP-097","111-CCH-IRP-065"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007632","name":"Changhua Christine Hospital","doi-asserted-by":"publisher","award":["MOST 108-2321-B-002-060-MY2","110-CCH-IRP-097","111-CCH-IRP-065"],"award-info":[{"award-number":["MOST 108-2321-B-002-060-MY2","110-CCH-IRP-097","111-CCH-IRP-065"]}],"id":[{"id":"10.13039\/501100007632","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Formoterol, a \u03b22-adrenergic receptor (\u03b22AR) agonist, shows promise in various diseases, but its effectiveness in Parkinson\u2019s disease (PD) is debated, with unclear regulation of mitochondrial homeostasis. This study employed a cell model featuring mitochondrial ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) variants associated with familial parkinsonism, demonstrating mitochondrial dysfunction and dynamic imbalance, exploring the therapeutic effects and underlying mechanisms of formoterol. Results revealed that 24-h formoterol treatment enhanced cell proliferation, viability, and neuroprotection against oxidative stress. Mitochondrial function, encompassing DNA copy number, repatriation, and complex III-linked respiration, was comprehensively restored, along with the dynamic rebalance of fusion\/fission events. Formoterol reduced extensive hypertubulation, in contrast to mitophagy, by significantly upregulating protein Drp-1, in contrast to fusion protein Mfn2, mitophagy-related protein Parkin. The upstream mechanism involved the restoration of ERK signaling and the inhibition of Akt overactivity, contingent on the activation of \u03b22-adrenergic receptors. Formoterol additionally aided in segregating healthy mitochondria for distribution and transport, therefore normalizing mitochondrial arrangement in mutant cells. This study provides preliminary evidence that formoterol offers neuroprotection, acting as a mitochondrial dynamic balance regulator, making it a promising therapeutic candidate for PD.<\/jats:p>","DOI":"10.3390\/biology13040231","type":"journal-article","created":{"date-parts":[[2024,3,31]],"date-time":"2024-03-31T13:32:56Z","timestamp":1711891976000},"page":"231","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Formoterol Acting via \u03b22-Adrenoreceptor Restores Mitochondrial Dysfunction Caused by Parkinson\u2019s Disease-Related UQCRC1 Mutation and Improves Mitochondrial Homeostasis Including Dynamic and Transport"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8349-862X","authenticated-orcid":false,"given":"Jui-Chih","family":"Chang","sequence":"first","affiliation":[{"name":"Center of Regenerative Medicine and Tissue Repair, Institute of ATP, Changhua Christian Hospital, Changhua 500, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huei-Shin","family":"Chang","sequence":"additional","affiliation":[{"name":"Center of Regenerative Medicine and Tissue Repair, Institute of ATP, Changhua Christian Hospital, Changhua 500, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Chun","family":"Chao","sequence":"additional","affiliation":[{"name":"Inflammation Research & Drug Development Center, Changhua Christian Hospital, Changhua 500, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7221-2895","authenticated-orcid":false,"given":"Ching-Shan","family":"Huang","sequence":"additional","affiliation":[{"name":"Center of Regenerative Medicine and Tissue Repair, Institute of ATP, Changhua Christian Hospital, Changhua 500, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8566-7573","authenticated-orcid":false,"given":"Chin-Hsien","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Taiwan University Hospital, Taipei 100, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhong-Sheng","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of General Research Laboratory of Research, Changhua Christian Hospital, Changhua 500, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui-Ju","family":"Chang","sequence":"additional","affiliation":[{"name":"Center of Regenerative Medicine and Tissue Repair, Institute of ATP, Changhua Christian Hospital, Changhua 500, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chin-San","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Changhua Christian Hospital, Changhua 500, Taiwan"},{"name":"Vascular and Genomic Center, Institute of ATP, Changhua Christian Hospital, Changhua 500, Taiwan"},{"name":"Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan"},{"name":"College of Medicine, National Chung Hsing University, Taichung 402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chieh-Sen","family":"Chuang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Changhua Christian Hospital, Changhua 500, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,30]]},"reference":[{"key":"ref_1","unstructured":"Billington, C.K., Penn, R.B., and Hall, I.P. 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