{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T03:09:13Z","timestamp":1791342553795,"version":"4.3.1"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,1,9]],"date-time":"2012-01-09T00:00:00Z","timestamp":1326067200000},"content-version":"vor","delay-in-days":1348,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology of the Cell"],"published-print":{"date-parts":[[2008,5]]},"abstract":"<jats:p><jats:italic>Background information<\/jats:italic>. Human OPA1 (optic atrophy type 1) is a dynamin\u2010related protein of the mitochondrial IMS (intermembrane space) involved in membrane fusion and remodelling. Similarly to its yeast orthologue Mgm1p that exists in two isoforms generated by the serine protease Pcp1p\/Rbd1p, OPA1 exists in various isoforms generated by alternative splicing and processing. In the present paper, we focus on protease processing of OPA1.<\/jats:p><jats:p><jats:italic>Results<\/jats:italic>. We find that various mammalian cell types display a similar pattern of OPA1 isoforms [two L\u2010OPA1 (long isoforms of OPA1) and three S\u2010OPA1 (short isoforms of OPA1)] and that loss of the inner membrane potential, but not inhibition of oxidative phosphorylation or glycolysis, induces rapid and complete processing of L\u2010OPA1 to S\u2010OPA1. In isolated mitochondria, OPA1 processing was inhibited by heavy\u2010metal chelators, pointing to processing by a mitochondrial metalloprotease. The pattern of OPA1 isoforms and its processing kinetics were normal in mitochondria devoid of the serine protease PARL (presenilins\u2010associated rhomboid\u2010like protein) \u2013 the human orthologue of Pcp1\/Rbd1 \u2013 and in cells from patients carrying homozygous mutations in <jats:italic>SPG7<\/jats:italic> (spastic paraplegia type 7), a gene encoding the matrix\u2010oriented metalloprotease paraplegin. In contrast, OPA1 processing kinetics were delayed upon knock\u2010down of YME1L (human yme1\u2010like protein), an IMS\u2010oriented metalloprotease. OPA1 processing was also stimulated during apoptosis, but inhibition of this processing did not affect apoptotic release of OPA1 and cytochrome <jats:italic>c<\/jats:italic>. Finally, we show that all OPA1 isoforms interact with Mfn1 (mitofusin 1) and Mfn2 and that these interactions are not affected by dissipation of \u0394\u03a8m (inner mitochondrial membrane potential) or OPA1 processing.<\/jats:p><jats:p><jats:italic>Conclusions<\/jats:italic>. Metalloprotease\u2010mediated processing of OPA1 is modulated by the inner membrane potential and is likely to be mediated by the YME1L protease.<\/jats:p>","DOI":"10.1042\/bc20070110","type":"journal-article","created":{"date-parts":[[2008,4,18]],"date-time":"2008-04-18T12:11:58Z","timestamp":1208520718000},"page":"315-325","source":"Crossref","is-referenced-by-count":163,"title":["Metalloprotease\u2010mediated OPA1 processing is modulated by the mitochondrial membrane potential"],"prefix":"10.1111","volume":"100","author":[{"given":"Olwenn","family":"Guillery","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Malka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Landes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Guillou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Blackstone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Lomb\u00e8s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Belenguer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien","family":"Arnoult","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Rojo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,1,9]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4889(02)00267-7"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M505970200"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81203-9"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200211046"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M503062200"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.06.021"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-001-0633-y"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M606059200"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e07-02-0164"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1099320"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M400920200"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200704112"},{"key":"e_1_2_7_14_1","doi-asserted-by":"crossref","unstructured":"GuilleryO.MalkaF.FrachonP.MileaD.RojoM.Lomb\u00e8sA.Modulation of mitochondrial morphology by bioenergetics defects in primary human fibroblastsNeuromuscul. 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