{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T08:31:09Z","timestamp":1779179469414,"version":"3.51.4"},"posted":{"date-parts":[[2023,1,18]]},"group-title":"Biophysics","reference-count":76,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,11,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Cristae membrane state plays a central role in regulating mitochondrial function and cellular metabolism. The protein Optic atrophy 1 (Opa1) is an important crista remodeler that exists as two forms in the mitochondrion, a membrane-anchored long form (l-Opa1) and a processed short form (s-Opa1). The mechanisms for how Opa1 influences cristae shape have remained unclear due to lack of native three-dimensional views of cristae. We perform\n                  <jats:italic>in situ<\/jats:italic>\n                  cryo-electron tomography of cryo-focused ion beam milled mouse embryonic fibroblasts with defined Opa1 states to understand how each form of Opa1 influences cristae architecture. In our tomograms, we observe a variety of cristae shapes with distinct trends dependent on s-Opa1:l-Opa1 balance. Increased l-Opa1 levels promote cristae stacking and elongated mitochondria while increased s-Opa1 levels correlated with irregular cristae packing and round mitochondria shape. Functional assays indicate a role for l-Opa1 in wild-type apoptotic and calcium handling responses, and compromised respiratory function under Opa1 imbalance. In summary, we provide three-dimensional visualization of cristae architecture to reveal relationships between mitochondrial ultrastructure and cellular function dependent on Opa1-mediated membrane remodeling.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>\n                        <jats:italic>In situ<\/jats:italic>\n                        ultrastructural characterization of mitochondrial cristae with different forms of Opa1.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Mitochondria with predominantly l-Opa1 show crista stacking, longer cristae, reduced globular cristae and an absence of tubular cristae.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Mitochondria with mostly s-Opa1 showed irregular cristae packing with wider cristae junctions and narrower cristae.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>l-Opa1 expressing cells with WT-like cristae junction properties, show wild-type apoptotic response and calcium handling.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Imbalance in Opa1 processing show compromised respiratory function and an increase in amorphous cristae.<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.1101\/2023.01.16.524176","type":"posted-content","created":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T06:15:12Z","timestamp":1674022512000},"source":"Crossref","is-referenced-by-count":8,"title":["<i>In situ<\/i>\n                  architecture of Opa1-dependent mitochondrial cristae remodeling"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3209-5492","authenticated-orcid":false,"given":"Michelle Y.","family":"Fry","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9123-1132","authenticated-orcid":false,"given":"Paula P.","family":"Navarro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9018-8179","authenticated-orcid":false,"given":"Pusparanee","family":"Hakim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5590-1170","authenticated-orcid":false,"given":"Virly 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