{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:03:24Z","timestamp":1791288204622,"version":"4.3.0"},"reference-count":57,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,12,13]],"date-time":"2006-12-13T00:00:00Z","timestamp":1165968000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2007,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To characterize the molecular links between type\u20101 autosomal dominant optic atrophy (ADOA) and OPA1 dysfunctions, the effects of pathogenic alleles of this dynamin on mitochondrial morphology and apoptosis were analyzed, either in fibroblasts from affected individuals, or in HeLa cells transfected with similar mutants. The alleles were missense substitutions in the GTPase domain (OPA1<jats:sup>G300E<\/jats:sup> and OPA1<jats:sup>R290Q<\/jats:sup>) or deletion of the GTPase effector domain (OPA1<jats:sup>\u039458<\/jats:sup>). Fragmentation of mitochondria and apoptosis increased in OPA1<jats:sup>R290Q<\/jats:sup> fibroblasts and in OPA1<jats:sup>G300E<\/jats:sup> transfected HeLa cells. OPA1<jats:sup>\u039458<\/jats:sup> did not influence mitochondrial morphology, but increased the sensitivity to staurosporine of fibroblasts. In these cells, the amount of OPA1 protein was half of that in control fibroblasts. We conclude that GTPase mutants exert a dominant negative effect by competing with wild\u2010type alleles to integrate into fusion\u2010competent complexes, whereas C\u2010terminal truncated alleles act by haplo\u2010insufficiency. We present a model where antagonistic fusion and fission forces maintain the mitochondrial network, within morphological limits that are compatible with cellular functions. In the retinal ganglion cells (RGCs) of patients suffering from type\u20101 ADOA, OPA1\u2010driven fusion cannot adequately oppose fission, thereby rendering them more sensitive to apoptotic stimuli and eventually leading to optic nerve degeneration. J. Cell. Physiol. 211: 423\u2013430, 2007. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.20950","type":"journal-article","created":{"date-parts":[[2006,12,13]],"date-time":"2006-12-13T17:51:23Z","timestamp":1166032283000},"page":"423-430","source":"Crossref","is-referenced-by-count":150,"title":["Effects of OPA1 mutations on mitochondrial morphology and apoptosis: Relevance to ADOA pathogenesis"],"prefix":"10.1002","volume":"211","author":[{"given":"Aur\u00e9lien","family":"Olichon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Landes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laetitia","family":"Arnaun\u00e9\u2010Pelloquin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent J.","family":"Emorine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Mils","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s","family":"Guichet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Delettre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Hamel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Amati\u2010Bonneau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Bonneau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Reynier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Lenaers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Belenguer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,12,13]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/79944"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.025502"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2003.024372"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/349117a0"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2003.10.003"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2004.05.009"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M503062200"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407043101"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.06.021"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.12.9.2578"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110119200"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/79936"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-001-0633-y"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/3.6.977"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20161"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(01)00055-7"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210285200"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M400920200"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2004.12.083"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.16.1.483"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(80)35247-0"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M303758200"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9394(79)90565-8"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401260"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.117.6.805"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000157282.76715.B1"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-3768.1983.tb01424.x"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0420.1996.tb00672.x"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e04-04-0294"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e02-06-0330"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/yea.901"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.11.003"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20278"},{"key":"e_1_2_6_35_1","volume-title":"Genetic risks","author":"Lyle W","year":"1990"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.39.8.e47"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/35065645"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109260200"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(02)02985-X"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C200677200"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.9539"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2005.02.005"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.10.12.4403"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1313"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2003.016576"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:MCBI.0000009879.01256.f6"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)02874-7"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(03)00070-X"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e02-12-0788"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/19024"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.144.4.711"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M408910200"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2004.09.026"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.eye.6701570"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.35.10.793"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200209015"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1299.037"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1341"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcp.20950","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.20950","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T17:27:44Z","timestamp":1697131664000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.20950"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,12,13]]},"references-count":57,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2007,5]]}},"alternative-id":["10.1002\/jcp.20950"],"URL":"https:\/\/doi.org\/10.1002\/jcp.20950","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,12,13]]}}}