{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T22:17:47Z","timestamp":1790201867763,"version":"4.1.0"},"reference-count":82,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"31","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2024,8,2]]},"abstract":"<jats:p>\n                    Mitochondrial fusion and fission accompany adaptive responses to stress and altered metabolic demands. Inner membrane fusion and cristae morphogenesis depends on optic atrophy 1 (Opa1), which is expressed in different isoforms and is cleaved from a membrane-bound, long to a soluble, short form. Here, we have analyzed the physiological role of Opa1 isoforms and Opa1 processing by generating mouse lines expressing only one cleavable Opa1 isoform or a non-cleavable variant thereof. Our results show that expression of a single cleavable or non-cleavable Opa1 isoform preserves embryonic development and the health of adult mice. Opa1 processing is dispensable under metabolic and thermal stress but prolongs life span and protects against mitochondrial cardiomyopathy in OXPHOS-deficient\n                    <jats:italic>Cox10<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. Mechanistically, loss of Opa1 processing disturbs the balance between mitochondrial biogenesis and mitophagy, suppressing cardiac hypertrophic growth in\n                    <jats:italic>Cox10<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    hearts. Our results highlight the critical regulatory role of Opa1 processing, mitochondrial dynamics, and metabolism for cardiac hypertrophy.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adp0443","type":"journal-article","created":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T13:58:41Z","timestamp":1722607121000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":25,"title":["Opa1 processing is dispensable in mouse development but is protective in mitochondrial cardiomyopathy"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7552-4843","authenticated-orcid":true,"given":"Sofia","family":"Ahola","sequence":"first","affiliation":[{"name":"Max Planck Institute for Biology of Ageing, Cologne, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9779-6361","authenticated-orcid":true,"given":"Lilli 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Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Gailus-Durner","sequence":"additional","affiliation":[{"name":"Institute of Experimental Genetics, German Mouse Clinic, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health (GmbH), Neuherberg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7898-2353","authenticated-orcid":true,"given":"Martin Hrabe","family":"de Angelis","sequence":"additional","affiliation":[{"name":"Institute of Experimental Genetics, German Mouse Clinic, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health (GmbH), Neuherberg, Germany."},{"name":"Experimental Genetics, TUM School of Life Sciences, Technische Universit\u00e4t M\u00fcnchen, Freising, Germany."},{"name":"German Center for Diabetes Research (DZD), 85764 Neuherberg."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2970-6894","authenticated-orcid":true,"given":"Dietmar","family":"Riedel","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Multidisciplinary Sciences, G\u00f6ttingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1560-5099","authenticated-orcid":true,"given":"Hendrik","family":"Nolte","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Biology of Ageing, Cologne, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1250-1462","authenticated-orcid":true,"given":"Thomas","family":"Langer","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Biology of Ageing, Cologne, Germany."},{"name":"Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 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