{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:12:40Z","timestamp":1790691160488,"version":"4.1.0"},"reference-count":78,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,4,13]],"date-time":"2021-04-13T00:00:00Z","timestamp":1618272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS092093"],"award-info":[{"award-number":["NS092093"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS086074"],"award-info":[{"award-number":["NS086074"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG062135"],"award-info":[{"award-number":["AG062135"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Alterations in mitochondrial function and morphology are associated with many human diseases, including cancer and neurodegenerative diseases. Mitochondrial impairment is linked to Parkinson\u2019s disease (PD) pathogenesis, and alterations in mitochondrial dynamics are seen in PD models. In particular, \u03b1-synuclein (\u03b1S) abnormalities are often associated with pathological changes to mitochondria. However, the relationship between \u03b1S pathology and mitochondrial dynamics remains poorly defined. Herein, we examined a mouse model of \u03b1-synucleinopathy for \u03b1S pathology-linked alterations in mitochondrial dynamics in vivo. We show that \u03b1-synucleinopathy in a transgenic (Tg) mouse model expressing familial PD-linked mutant A53T human \u03b1S (TgA53T) is associated with a decrease in Drp1 localization and activity in the mitochondria. In addition, we show that the loss of Drp1 function in the mitochondria is associated with two distinct phenotypes of enlarged neuronal mitochondria. Mitochondrial enlargement was only present in diseased animals and, apart from Drp1, other proteins involved in mitochondrial dynamics are unlikely to cause these changes, as their levels remained mostly unchanged. Further, the levels of Mfn1, a protein that facilitates mitochondrial fusion, was decreased nonspecifically with transgene expression. These results support the view that altered mitochondrial dynamics are a significant neuropathological factor in \u03b1-synucleinopathies.<\/jats:p>","DOI":"10.3390\/cells10040885","type":"journal-article","created":{"date-parts":[[2021,4,13]],"date-time":"2021-04-13T10:58:07Z","timestamp":1618311487000},"page":"885","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Changes in Drp1 Function and Mitochondrial Morphology Are Associated with the \u03b1-Synuclein Pathology in a Transgenic Mouse Model of Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"10","author":[{"given":"Philipp","family":"Portz","sequence":"first","affiliation":[{"name":"Department of Medical Cell Biology, Institute for Anatomy and Cell Biology, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5865-9682","authenticated-orcid":false,"given":"Michael K.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Institute for Translational Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/S1474-4422(06)70471-9","article-title":"Epidemiology of parkinson\u2019s disease","volume":"5","author":"Breteler","year":"2006","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1002\/mds.26424","article-title":"Mds clinical diagnostic criteria for parkinson\u2019s disease","volume":"30","author":"Postuma","year":"2015","journal-title":"Mov. 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