{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T21:47:31Z","timestamp":1793051251316,"version":"4.5.0"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T00:00:00Z","timestamp":1641168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1191770 1150677 1191151"],"award-info":[{"award-number":["1191770 1150677 1191151"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1-HL142271"],"award-info":[{"award-number":["RO1-HL142271"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G1002570"],"award-info":[{"award-number":["G1002570"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018956","name":"NIHR Cambridge Biomedical Research Centre","doi-asserted-by":"publisher","award":["BRC-1215-20014"],"award-info":[{"award-number":["BRC-1215-20014"]}],"id":[{"id":"10.13039\/501100018956","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Autosomal Dominant Optic Atrophy (ADOA), a disease that causes blindness and other neurological disorders, is linked to <jats:italic>OPA1<\/jats:italic> mutations. OPA1, dependent on its GTPase and GED domains, governs inner mitochondrial membrane (IMM) fusion and cristae organization, which are central to oxidative metabolism. Mitochondrial dynamics and IMM organization have also been implicated in Ca<jats:sup>2+<\/jats:sup> homeostasis and signaling but the specific involvements of OPA1 in Ca<jats:sup>2+<\/jats:sup> dynamics remain to be established. Here we studied the possible outcomes of OPA1 and its ADOA-linked mutations in Ca<jats:sup>2+<\/jats:sup> homeostasis using rescue and overexpression strategies in <jats:italic>Opa1<\/jats:italic>-deficient and <jats:italic>wild-type<\/jats:italic> murine embryonic fibroblasts (MEFs), respectively and in human ADOA-derived fibroblasts. MEFs lacking <jats:italic>Opa1<\/jats:italic> required less Ca<jats:sup>2+<\/jats:sup> mobilization from the endoplasmic reticulum (ER) to induce a mitochondrial matrix [Ca<jats:sup>2+<\/jats:sup>] rise ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>mito<\/jats:sub>). This was associated with closer ER-mitochondria contacts and no significant changes in the mitochondrial calcium uniporter complex. Patient cells carrying <jats:italic>OPA1<\/jats:italic> GTPase or GED domain mutations also exhibited altered Ca<jats:sup>2+<\/jats:sup> homeostasis, and the mutations associated with lower OPA1 levels displayed closer ER-mitochondria gaps. Furthermore, in <jats:italic>Opa1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> MEF background, we found that acute expression of <jats:italic>OPA1<\/jats:italic> GTPase mutants but no GED mutants, partially restored cytosolic [Ca<jats:sup>2+<\/jats:sup>] ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyto<\/jats:sub>) needed for a prompt [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>mito<\/jats:sub> rise. Finally, <jats:italic>OPA1<\/jats:italic> mutants\u2019 overexpression in WT MEFs disrupted Ca<jats:sup>2+<\/jats:sup> homeostasis, partially recapitulating the observations in ADOA patient cells. Thus, OPA1 modulates functional ER-mitochondria coupling likely through the OPA1 GED domain in <jats:italic>Opa1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> MEFs. However, the co-existence of WT and mutant forms of OPA1 in patients promotes an imbalance of Ca<jats:sup>2+<\/jats:sup> homeostasis without a domain-specific effect, likely contributing to the overall ADOA progress.<\/jats:p>","DOI":"10.3389\/fcell.2021.774108","type":"journal-article","created":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T08:56:00Z","timestamp":1641200160000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":42,"title":["OPA1 Modulates Mitochondrial Ca2+ Uptake Through ER-Mitochondria Coupling"],"prefix":"10.3389","volume":"9","author":[{"given":"Benjam\u00edn","family":"Cartes-Saavedra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josefa","family":"Macuada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Lagos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duxan","family":"Arancibia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda E.","family":"Andr\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Yu-Wai-Man","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gy\u00f6rgy","family":"Hajn\u00f3czky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ver\u00f3nica","family":"Eisner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1111\/j.1471-4159.2008.05401.x","article-title":"Characterization of OPA1 Isoforms Isolated from Mouse Tissues","volume":"106","author":"Akepati","year":"2008","journal-title":"J. Neurochem."},{"key":"B2","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1093\/brain\/awm298","article-title":"OPA1 Mutations Induce Mitochondrial DNA Instability and Optic Atrophy 'plus' Phenotypes","volume":"131","author":"Amati-Bonneau","year":"2008","journal-title":"Brain"},{"key":"B3","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1038\/nature10234","article-title":"Integrative Genomics Identifies MCU as an Essential Component of the Mitochondrial Calcium Uniporter","volume":"476","author":"Baughman","year":"2011","journal-title":"Nature"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1152\/physrev.00006.2016","article-title":"The Inositol Trisphosphate\/Calcium Signaling Pathway in Health and Disease","volume":"96","author":"Berridge","year":"2016","journal-title":"Physiol. Rev."},{"key":"B5","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.ceca.2016.05.001","article-title":"Subcellular ROS Imaging Methods: Relevance for the Study of Calcium Signaling","volume":"60","author":"Booth","year":"2016","journal-title":"Cell Calcium"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e003012","DOI":"10.1161\/JAHA.112.003012","article-title":"OPA1 Mutation and Late-Onset Cardiomyopathy: Mitochondrial Dysfunction and mtDNA Instability","volume":"1","author":"Chen","year":"2012","journal-title":"J. Am. Heart Assoc."},{"key":"B7","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/j.cell.2013.08.032","article-title":"Mitochondrial Cristae Shape Determines Respiratory Chain Supercomplexes Assembly and Respiratory Efficiency","volume":"155","author":"Cogliati","year":"2013","journal-title":"Cell"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2194","DOI":"10.1038\/s41418-021-00747-6","article-title":"Deletion of the Mitochondria-Shaping Protein Opa1 during Early Thymocyte Maturation Impacts Mature Memory T Cell Metabolism","volume":"28","author":"Corrado","year":"2021","journal-title":"Cell Death Differ"},{"key":"B9","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1016\/j.cmet.2013.04.020","article-title":"MICU1 Controls Both the Threshold and Cooperative Activation of the Mitochondrial Ca2+ Uniporter","volume":"17","author":"Csord\u00e1s","year":"2013","journal-title":"Cell Metab"},{"key":"B10","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1083\/jcb.200604016","article-title":"Structural and Functional Features and Significance of the Physical Linkage between ER and Mitochondria","volume":"174","author":"Csord\u00e1s","year":"2006","journal-title":"J. Cel Biol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1093\/emboj\/18.1.96","article-title":"Quasi-synaptic Calcium Signal Transmission between Endoplasmic Reticulum and Mitochondria","volume":"18","author":"Csord\u00e1s","year":"1999","journal-title":"EMBO J."},{"key":"B12","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.molcel.2010.06.029","article-title":"Imaging Interorganelle Contacts and Local Calcium Dynamics at the ER-Mitochondrial Interface","volume":"39","author":"Csord\u00e1s","year":"2010","journal-title":"Mol. Cel"},{"key":"B13","doi-asserted-by":"publisher","first-page":"53","DOI":"10.3109\/13816811003698117","article-title":"Characterization of Ca2+Signalling in Postnatal Mouse Retinal Ganglion Cells: Involvement of OPA1 in Ca2+Clearance","volume":"31","author":"Dayanithi","year":"2010","journal-title":"Ophthalmic Genet."},{"key":"B14","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1038\/nature10230","article-title":"A Forty-Kilodalton Protein of the Inner Membrane Is the Mitochondrial Calcium Uniporter","volume":"476","author":"De Stefani","year":"2011","journal-title":"Nature"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2557","DOI":"10.1016\/j.celrep.2017.05.073","article-title":"OPA1 Isoforms in the Hierarchical Organization of Mitochondrial Functions","volume":"19","author":"Del Dotto","year":"2017","journal-title":"Cel Rep."},{"key":"B16","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1038\/79936","article-title":"Nuclear Gene OPA1, Encoding a Mitochondrial Dynamin-Related Protein, Is Mutated in Dominant Optic Atrophy","volume":"26","author":"Delettre","year":"2000","journal-title":"Nat. Genet."},{"key":"B17","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1146\/annurev.ph.52.030190.002315","article-title":"Ca2+ as A Second Messenger within Mitochondria of the Heart and Other Tissues","volume":"52","author":"Denton","year":"1990","journal-title":"Annu. Rev. Physiol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1083\/jcb.200906098","article-title":"Coassembly of Mgm1 Isoforms Requires Cardiolipin and Mediates Mitochondrial Inner Membrane Fusion","volume":"186","author":"DeVay","year":"2009","journal-title":"J. Cel Biol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1083\/jcb.201312066","article-title":"Mitochondrial Fusion Is Frequent in Skeletal Muscle and Supports Excitation-Contraction Coupling","volume":"205","author":"Eisner","year":"2014","journal-title":"J. Cel Biol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1038\/s41556-018-0133-0","article-title":"Mitochondrial Dynamics in Adaptive and Maladaptive Cellular Stress Responses","volume":"20","author":"Eisner","year":"2018","journal-title":"Nat. Cel Biol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.cell.2006.06.025","article-title":"OPA1 Controls Apoptotic Cristae Remodeling Independently from Mitochondrial Fusion","volume":"126","author":"Frezza","year":"2006","journal-title":"Cell"},{"key":"B22","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.ceca.2014.11.008","article-title":"Mitochondrial Ca2+ Uptake Correlates with the Severity of the Symptoms in Autosomal Dominant Optic Atrophy","volume":"57","author":"F\u00fcl\u00f6p","year":"2015","journal-title":"Cell Calcium"},{"key":"B23","doi-asserted-by":"publisher","first-page":"e25199","DOI":"10.1371\/journal.pone.0025199","article-title":"The Effect of OPA1 on Mitochondrial Ca2+ Signaling","volume":"6","author":"F\u00fcl\u00f6p","year":"2011","journal-title":"PLoS One"},{"key":"B24","doi-asserted-by":"publisher","first-page":"3024","DOI":"10.1016\/j.celrep.2016.11.049","article-title":"Optic Atrophy 1 Is Epistatic to the Core MICOS Component MIC60 in Mitochondrial Cristae Shape Control","volume":"17","author":"Glytsou","year":"2016","journal-title":"Cel Rep."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1820","DOI":"10.1016\/j.cmet.2021.07.008","article-title":"Mitochondrial Cristae-Remodeling Protein OPA1 in POMC Neurons Couples Ca2+ Homeostasis with Adipose Tissue Lipolysis","volume":"33","author":"G\u00f3mez-Valad\u00e9s","year":"2021","journal-title":"Cel Metab"},{"key":"B26","doi-asserted-by":"publisher","first-page":"3732","DOI":"10.1038\/s41467-019-11692-x","article-title":"MICU1 Controls Cristae junction and Spatially Anchors Mitochondrial Ca2+ Uniporter Complex","volume":"10","author":"Gottschalk","year":"2019","journal-title":"Nat. Commun."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1007\/s00424-018-2133-0","article-title":"Intracellular Ca2+ Release Decelerates Mitochondrial Cristae Dynamics within the Junctions to the Endoplasmic Reticulum","volume":"470","author":"Gottschalk","year":"2018","journal-title":"Pflugers Arch. - Eur. J. Physiol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.1016\/j.bbabio.2008.12.011","article-title":"Characteristics and Possible Functions of Mitochondrial Ca2+ Transport Mechanisms","volume":"1787","author":"Gunter","year":"2009","journal-title":"Biochim. Biophys. Acta (Bba) - Bioenerg."},{"key":"B29","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.ceb.2014.06.002","article-title":"Reliance of ER\u2013Mitochondrial Calcium Signaling on Mitochondrial EF-Hand Ca2+ Binding Proteins: Miros, MICUs, LETM1 and Solute Carriers","volume":"29","author":"Hajn\u00f3czky","year":"2014","journal-title":"Curr. Opin. Cel Biol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/0092-8674(95)90430-1","article-title":"Decoding of Cytosolic Calcium Oscillations in the Mitochondria","volume":"82","author":"Hajn\u00f3czky","year":"1995","journal-title":"Cell"},{"key":"B31","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1016\/j.cmet.2020.04.007","article-title":"Developmental and Tumor Angiogenesis Requires the Mitochondria-Shaping Protein Opa1","volume":"31","author":"Herkenne","year":"2020","journal-title":"Cel Metab."},{"key":"B32","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1038\/s41419-020-03152-y","article-title":"OPA1 and MICOS Regulate Mitochondrial Crista Dynamics and Formation","volume":"11","author":"Hu","year":"2020","journal-title":"Cell Death Dis"},{"key":"B33","doi-asserted-by":"publisher","first-page":"13807","DOI":"10.1073\/pnas.96.24.13807","article-title":"Regulation of Mitochondrial ATP Synthesis by Calcium: Evidence for a Long-Term Metabolic Priming","volume":"96","author":"Jouaville","year":"1999","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.15252\/embr.201643748","article-title":"High\u2010affinity Cooperative Ca 2+ Binding by MICU 1- MICU 2 Serves as an On-Off Switch for the Uniporter","volume":"18","author":"Kamer","year":"2017","journal-title":"EMBO Rep."},{"key":"B35","doi-asserted-by":"publisher","first-page":"e49776","DOI":"10.15252\/embr.201949776","article-title":"Cristae Undergo Continuous Cycles of Membrane Remodelling in a MICOS-dependent Manner","volume":"21","author":"Kondadi","year":"2020","journal-title":"EMBO Rep."},{"key":"B36","doi-asserted-by":"publisher","first-page":"13176","DOI":"10.1096\/fj.201901136r","article-title":"Mitochondrial Morphology Regulates Organellar Ca2+uptake and Changes Cellular Ca2+homeostasis","volume":"33","author":"Kowaltowski","year":"2019","journal-title":"FASEB J."},{"key":"B37","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1038\/cdd.2012.128","article-title":"Loss of OPA1 Disturbs Cellular Calcium Homeostasis and Sensitizes for Excitotoxicity","volume":"20","author":"Kushnareva","year":"2013","journal-title":"Cel Death Differ"},{"key":"B38","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1016\/j.semcdb.2009.12.012","article-title":"OPA1 (Dys)functions","volume":"21","author":"Landes","year":"2010","journal-title":"Semin. Cel Develop. Biol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"D1062","DOI":"10.1093\/nar\/gkx1153","article-title":"ClinVar: Improving Access to Variant Interpretations and Supporting Evidence","volume":"46","author":"Landrum","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"e0164066","DOI":"10.1371\/journal.pone.0164066","article-title":"Increase in Cardiac Ischemia-Reperfusion Injuries in Opa1+\/- Mouse Model","volume":"11","author":"Le Page","year":"2016","journal-title":"PLoS One"},{"key":"B41","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1186\/s13023-019-1187-1","article-title":"OPA1: 516 Unique Variants and 831 Patients Registered in an Updated Centralized Variome Database","volume":"14","author":"Le Roux","year":"2019","journal-title":"Orphanet J. Rare Dis."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1016\/j.celrep.2016.07.011","article-title":"MICU1 Serves as a Molecular Gatekeeper to Prevent In Vivo Mitochondrial Calcium Overload","volume":"16","author":"Liu","year":"2016","journal-title":"Cel Rep."},{"key":"B43","doi-asserted-by":"publisher","first-page":"3074","DOI":"10.1038\/emboj.2009.255","article-title":"Mitochondrial 'kiss-And-Run': Interplay between Mitochondrial Motility and Fusion-Fission Dynamics","volume":"28","author":"Liu","year":"2009","journal-title":"EMBO J."},{"key":"B44","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1016\/j.cell.2012.10.011","article-title":"MICU1 Is an Essential Gatekeeper for MCU-Mediated Mitochondrial Ca2+ Uptake that Regulates Cell Survival","volume":"151","author":"Mallilankaraman","year":"2012","journal-title":"Cell"},{"key":"B45","doi-asserted-by":"publisher","first-page":"7743","DOI":"10.1074\/jbc.c200677200","article-title":"Loss of OPA1 Perturbates the Mitochondrial Inner Membrane Structure and Integrity, Leading to Cytochrome C Release and Apoptosis","volume":"278","author":"Olichon","year":"2003","journal-title":"J. Biol. Chem."},{"key":"B46","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1038\/sj.cdd.4402048","article-title":"OPA1 Alternate Splicing Uncouples an Evolutionary Conserved Function in Mitochondrial Fusion from a Vertebrate Restricted Function in Apoptosis","volume":"14","author":"Olichon","year":"","journal-title":"Cel Death Differ"},{"key":"B47","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1002\/jcp.20950","article-title":"Effects of OPA1 Mutations on Mitochondrial Morphology and Apoptosis: Relevance to ADOA Pathogenesis","volume":"211","author":"Olichon","year":"","journal-title":"J. Cel. Physiol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1016\/j.molcel.2014.01.013","article-title":"MICU1 and MICU2 Finely Tune the Mitochondrial Ca2+ Uniporter by Exerting Opposite Effects on MCU Activity","volume":"53","author":"Patron","year":"2014","journal-title":"Mol. Cel"},{"key":"B49","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1038\/s41418-018-0113-8","article-title":"MICU3 Is a Tissue-specific Enhancer of Mitochondrial Calcium Uptake","volume":"26","author":"Patron","year":"2019","journal-title":"Cel Death Differ"},{"key":"B50","doi-asserted-by":"publisher","first-page":"2676","DOI":"10.15252\/embj.201488349","article-title":"OPA1\u2010dependent Cristae Modulation Is Essential for Cellular Adaptation to Metabolic Demand","volume":"33","author":"Patten","year":"2014","journal-title":"EMBO J."},{"key":"B51","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1038\/nature09358","article-title":"MICU1 Encodes a Mitochondrial EF Hand Protein Required for Ca2+ Uptake","volume":"467","author":"Perocchi","year":"2010","journal-title":"Nature"},{"key":"B67","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1093\/cvr\/cvs117","article-title":"Down-Regulation of OPA1 Alters Mouse Mitochondrial Morphology, PTP Function, and Cardiac Adaptation to Pressure Overload","volume":"94","author":"Piquereau","year":"2012","journal-title":"Cardiovasc. Res."},{"key":"B52","doi-asserted-by":"publisher","first-page":"2362","DOI":"10.1038\/emboj.2013.157","article-title":"The Mitochondrial Calcium Uniporter Is a Multimer that Can Include a Dominant-Negative Pore-Forming Subunit","volume":"32","author":"Raffaello","year":"2013","journal-title":"EMBO J."},{"key":"B53","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1038\/nrm3412","article-title":"Mitochondria as Sensors and Regulators of Calcium Signalling","volume":"13","author":"Rizzuto","year":"2012","journal-title":"Nat. Rev. Mol. Cel Biol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1763","DOI":"10.1126\/science.280.5370.1763","article-title":"Close Contacts with the Endoplasmic Reticulum as Determinants of Mitochondrial Ca 2+ Responses","volume":"280","author":"Rizzuto","year":"1998","journal-title":"Science"},{"key":"B55","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1128\/mcb.01483-13","article-title":"SIRT3 Deacetylates and Activates OPA1 to Regulate Mitochondrial Dynamics during Stress","volume":"34","author":"Samant","year":"2014","journal-title":"Mol. Cel. Biol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1126\/science.1242993","article-title":"EMRE Is an Essential Component of the Mitochondrial Calcium Uniporter Complex","volume":"342","author":"Sancak","year":"2013","journal-title":"Science"},{"key":"B57","doi-asserted-by":"publisher","first-page":"3525","DOI":"10.1091\/mbc.e09-03-0252","article-title":"Mitofusins and OPA1 Mediate Sequential Steps in Mitochondrial Membrane Fusion","volume":"20","author":"Song","year":"2009","journal-title":"MBoC"},{"key":"B58","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1016\/j.bbamcr.2006.04.002","article-title":"Mitochondrial Dynamics and Ca2+ Signaling","volume":"1763","author":"Szabadkai","year":"2006","journal-title":"Biochim. Biophys. Acta (Bba) - Mol. Cel Res."},{"key":"B59","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.molcel.2004.09.026","article-title":"Drp-1-dependent Division of the Mitochondrial Network Blocks Intraorganellar Ca2+ Waves and Protects against Ca2+-Mediated Apoptosis","volume":"16","author":"Szabadkai","year":"2004","journal-title":"Mol. Cel"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1101\/803213","article-title":"MICU1 Regulates Mitochondrial Cristae Structure and Function Independent of the Mitochondrial Calcium Uniporter Channel","author":"Tomar","year":"2019","journal-title":"BioRxiv"},{"key":"B61","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1016\/j.cmet.2015.05.007","article-title":"The OPA1-dependent Mitochondrial Cristae Remodeling Pathway Controls Atrophic, Apoptotic, and Ischemic Tissue Damage","volume":"21","author":"Varanita","year":"2015","journal-title":"Cel Metab."},{"key":"B62","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1083\/jcb.200605138","article-title":"Dynamic Subcompartmentalization of the Mitochondrial Inner Membrane","volume":"175","author":"Vogel","year":"2006","journal-title":"J. Cel Biol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1136\/jmg.35.10.793","article-title":"Clinical Features, Molecular Genetics, and Pathophysiology of Dominant Optic Atrophy","volume":"35","author":"Votruba","year":"1998","journal-title":"J. Med. Genet."},{"key":"B64","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1038\/nprot.2010.43","article-title":"Detection of Mycoplasma in Cell Cultures","volume":"5","author":"Young","year":"2010","journal-title":"Nat. Protoc."},{"key":"B65","doi-asserted-by":"publisher","first-page":"4029","DOI":"10.1038\/s41467-020-17821-1","article-title":"Inhibition of Autophagy Curtails Visual Loss in a Model of Autosomal Dominant Optic Atrophy","volume":"11","author":"Zaninello","year":"2020","journal-title":"Nat. Commun."},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-021-00847-3","article-title":"Sustained Intracellular Calcium Rise Mediates Neuronal Mitophagy in Models of Autosomal Dominant Optic Atrophy","author":"Zaninello","year":"2021","journal-title":"Cel Death Differ"}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.774108\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T08:56:07Z","timestamp":1641200167000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.774108\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,3]]},"references-count":67,"alternative-id":["10.3389\/fcell.2021.774108"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2021.774108","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,3]]},"article-number":"774108"}}