{"doi":"10.1101/2023.01.16.524176","title":"<i>In situ</i> architecture of Opa1-dependent mitochondrial cristae remodeling","abstract":"Abstract 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 in situ 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. Highlights In situ ultrastructural characterization of mitochondrial cristae with different forms of Opa1. Mitochondria with predominantly l-Opa1 show crista stacking, longer cristae, reduced globular cristae and an absence of tubular cristae. Mitochondria with mostly s-Opa1 showed irregular cristae packing with wider cristae junctions and narrower cristae. l-Opa1 expressing cells with WT-like cristae junction properties, show wild-type apoptotic response and calcium handling. Imbalance in Opa1 processing show compromised respiratory function and an increase in amorphous cristae.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":390479,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9518,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":648331,"name":"Paula P. Navarro","orcid":"0000-0002-9123-1132","position":1,"is_corresponding":false},{"id":1162260,"name":"Pusparanee Hakim","orcid":"0000-0002-9018-8179","position":2,"is_corresponding":false},{"id":815196,"name":"Ananda VY","orcid":"0000-0001-5590-1170","position":3,"is_corresponding":false},{"id":650938,"name":"Xingping Qin","orcid":"0000-0003-3263-0843","position":4,"is_corresponding":false},{"id":1162261,"name":"Juan C. Landoni","orcid":"0000-0002-0318-6707","position":5,"is_corresponding":false},{"id":105003,"name":"Sneha Rath","orcid":"0000-0001-8839-1285","position":6,"is_corresponding":false},{"id":471932,"name":"Zintis Inde","orcid":"0000-0001-5564-1698","position":7,"is_corresponding":false},{"id":648332,"name":"Camila Makhlouta Lugo","orcid":"0000-0003-4655-8096","position":8,"is_corresponding":false},{"id":1162262,"name":"Bridget E Luce","orcid":"0000-0002-0107-5181","position":9,"is_corresponding":false},{"id":759735,"name":"Yifan Ge","orcid":"0000-0001-9135-9569","position":10,"is_corresponding":false},{"id":1162263,"name":"Julie L. McDonald","orcid":"0000-0002-3715-9619","position":11,"is_corresponding":false},{"id":1162264,"name":"Ilzat Ali","orcid":"0000-0003-2019-5645","position":12,"is_corresponding":false},{"id":1034570,"name":"Leillani L. Ha","orcid":"0000-0003-4478-660X","position":13,"is_corresponding":false},{"id":44843,"name":"Benjamin P. Kleinstiver","orcid":"0000-0002-5469-0655","position":14,"is_corresponding":false},{"id":286567,"name":"David C. Chan","orcid":"0000-0002-0191-2154","position":15,"is_corresponding":false},{"id":650944,"name":"Kristopher A. Sarosiek","orcid":"0000-0002-4618-5085","position":16,"is_corresponding":false},{"id":324094,"name":"Luke H. Chao","orcid":"0000-0002-4849-4148","position":17,"is_corresponding":false},{"id":673729,"name":"Michelle Y. Fry","orcid":"0000-0002-3209-5492","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-19T01:18:37.743462Z","pmid":"36711707","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}