{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:49:08Z","timestamp":1791298148663,"version":"4.1.0"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"38","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,9,23]]},"abstract":"\n Mutations in\n PTEN-induced kinase 1<\/jats:italic>\n (\n pink1<\/jats:italic>\n ) or\n parkin<\/jats:italic>\n cause autosomal-recessive and some sporadic forms of Parkinson's disease.\n pink1<\/jats:italic>\n acts upstream of\n parkin<\/jats:italic>\n in a common genetic pathway to regulate mitochondrial integrity in\n Drosophila<\/jats:italic>\n . Mitochondrial morphology is maintained by a dynamic balance between the opposing actions of mitochondrial fusion, controlled by\n Mitofusin<\/jats:italic>\n (\n mfn<\/jats:italic>\n ) and\n Optic atrophy 1<\/jats:italic>\n (\n opa1<\/jats:italic>\n ), and mitochondrial fission, controlled by\n drp1<\/jats:italic>\n . Here, we explore interactions between\n pink1<\/jats:italic>\n \/\n parkin<\/jats:italic>\n and the mitochondrial fusion\/fission machinery. Muscle-specific knockdown of the fly homologue of\n Mfn<\/jats:italic>\n (\n Marf<\/jats:italic>\n ) or\n opa1<\/jats:italic>\n , or overexpression of\n drp1<\/jats:italic>\n , results in significant mitochondrial fragmentation.\n Mfn<\/jats:italic>\n -knockdown flies also display altered cristae morphology. Interestingly, knockdown of\n Mfn<\/jats:italic>\n or\n opa1<\/jats:italic>\n or overexpression of\n drp1<\/jats:italic>\n , rescues the phenotypes of muscle degeneration, cell death, and mitochondrial abnormalities in\n pink1<\/jats:italic>\n or\n parkin<\/jats:italic>\n mutants. In the male germline, we also observe genetic interactions between\n pink1<\/jats:italic>\n and the testes-specific\n mfn<\/jats:italic>\n homologue\n fuzzy onion<\/jats:italic>\n , and between\n pink1<\/jats:italic>\n and\n drp1<\/jats:italic>\n . Our data suggest that the\n pink1<\/jats:italic>\n \/\n parkin<\/jats:italic>\n pathway promotes mitochondrial fission and\/or inhibits fusion by negatively regulating\n mfn<\/jats:italic>\n and\n opa1<\/jats:italic>\n function, and\/or positively regulating\n drp1<\/jats:italic>\n . However,\n pink1<\/jats:italic>\n and\n parkin<\/jats:italic>\n mutant flies show distinct mitochondrial phenotypes from\n drp1<\/jats:italic>\n mutant flies, and flies carrying a heterozygous mutation in\n drp1<\/jats:italic>\n enhance the\n pink1<\/jats:italic>\n -null phenotype, resulting in lethality. These results suggest that\n pink1<\/jats:italic>\n and\n parkin<\/jats:italic>\n are likely not core components of the\n drp1<\/jats:italic>\n -mediated mitochondrial fission machinery. Modification of fusion and fission may represent a novel therapeutic strategy for Parkinson's disease.\n <\/jats:p>","DOI":"10.1073\/pnas.0803998105","type":"journal-article","created":{"date-parts":[[2008,9,17]],"date-time":"2008-09-17T21:24:48Z","timestamp":1221686688000},"page":"14503-14508","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":631,"title":["The Parkinson's disease genes\n pink1<\/i>\n and\n parkin<\/i>\n promote mitochondrial fission and\/or inhibit fusion in\n Drosophila<\/i>"],"prefix":"10.1073","volume":"105","author":[{"given":"Hansong","family":"Deng","sequence":"first","affiliation":[{"name":"Departments of *Neurology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark W.","family":"Dodson","sequence":"additional","affiliation":[{"name":"Departments of *Neurology and"},{"name":"Molecular Biology Institute, University of California, Los Angeles, CA 90095; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixia","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Biology, California Institute of Technology, Pasadena, CA 91125"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Guo","sequence":"additional","affiliation":[{"name":"Departments of *Neurology and"},{"name":"Pharmacology and"},{"name":"Brain Research Institute, David Geffen School of Medicine, and"},{"name":"Molecular Biology Institute, University of California, Los Angeles, CA 90095; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,9,23]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00568-3"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6823561"},{"key":"e_1_3_4_3_2","first-page":"192","article-title":"Environment, mitochondria, and Parkinson's disease","volume":"8","author":"Sherer TB","year":"2002","unstructured":"TB Sherer, R Betarbet, JT Greenamyre, Environment, mitochondria, and Parkinson's disease. Neuroscientist 8, 192\u2013197 (2002).","journal-title":"Neuroscientist"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2007.04.010"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2006.09.007"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/33416"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1096284"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000167546.39375.82"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20256"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04779"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04788"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0602493103"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0737556100"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0719-07.2007"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.38.072902.093019"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2275"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.76.071905.090048"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80319-0"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(02)00141-7"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0040006"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.06.018"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2006.10.038"},{"key":"e_1_3_4_23_2","first-page":"71","volume-title":"The Development of Drosophila Melanogaster","author":"Fuller MT","year":"1993","unstructured":"MT Fuller, Spermatogenesis. The Development of Drosophila Melanogaster, eds A Martinez-Arias, M Bate (Cold Spring Harbor Lab Press, Cold Spring Harbor, NY), pp. 71\u2013147 (1993)."},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.118.2.401"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01095"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0709336105"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi377"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl114"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0500617102"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(199905)45:5<668::AID-ANA19>3.0.CO;2-Z"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.32.20150"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.115.8.1663"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/13014"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(01)00055-7"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.151.2.367"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5321.2045"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1090278"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1138595"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm305"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0803998105","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T16:50:35Z","timestamp":1649782235000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0803998105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,9,23]]},"references-count":39,"journal-issue":{"issue":"38","published-print":{"date-parts":[[2008,9,23]]}},"alternative-id":["10.1073\/pnas.0803998105"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0803998105","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1123406.580576","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,9,23]]},"assertion":[{"value":"2008-04-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-09-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}