{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T12:14:14Z","timestamp":1791980054933,"version":"4.4.0"},"reference-count":95,"publisher":"The Company of Biologists","issue":"18","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100009983","name":"Center for Molecular Medicine Cologne","doi-asserted-by":"crossref","award":["CAP14"],"award-info":[{"award-number":["CAP14"]}],"id":[{"id":"10.13039\/501100009983","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100009983","name":"Center for Molecular Medicine Cologne","doi-asserted-by":"crossref","award":["RPA02"],"award-info":[{"award-number":["RPA02"]}],"id":[{"id":"10.13039\/501100009983","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003390","name":"Fritz Thyssen Foundation","doi-asserted-by":"crossref","award":["10.15.1.018MN"],"award-info":[{"award-number":["10.15.1.018MN"]}],"id":[{"id":"10.13039\/501100003390","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100008454","name":"Boehringer Ingelheim Foundation","doi-asserted-by":"crossref","award":["Plus 3 program"],"award-info":[{"award-number":["Plus 3 program"]}],"id":[{"id":"10.13039\/501100008454","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["SPP2453"],"award-info":[{"award-number":["SPP2453"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["CRC 1218 TP A03"],"award-info":[{"award-number":["CRC 1218 TP A03"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["541758846"],"award-info":[{"award-number":["541758846"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100016888","name":"Bayer Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100016888","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100008001","name":"University of Cologne","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008001","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>The neuropathy Charcot\u2013Marie\u2013Tooth (CMT) is an incurable disease with a lack of genotype\u2013phenotype correlation. Variants of the mitochondrial protein mitofusin 2 (MFN2), a large GTPase that mediates mitochondrial fusion, are responsible for the subtype CMT type 2A (CMT2A). Interestingly, beyond membrane remodelling, additional roles of MFN2 have been identified, expanding the possibilities to explore its involvement in disease. Here, we investigated how cellular functions of MFN2 are associated with variants present in individuals with CMT2A. Using human cellular models, we observed that cells expressing CMT2A variants display increased endoplasmic reticulum (ER) stress and apoptotic cell death. Increased cleavage of PARP1, caspase 9, caspase 7 and caspase 3, alongside BAX translocation to mitochondria, pointed towards effects on intrinsic apoptosis. Moreover, although disruption of fusion and fission dynamics per se did not correlate with cell death markers, expression of MFN1 or MFN2 alleviated the apoptosis markers of CMT2A variant cell lines. In sum, our results highlight excessive cell death by intrinsic apoptosis as a potential target in CMT2A disease.<\/jats:p>","DOI":"10.1242\/jcs.263691","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T09:59:02Z","timestamp":1758794342000},"source":"Crossref","is-referenced-by-count":3,"title":["Charcot\u2013Marie\u2013Tooth type 2A variants of mitofusin 2 sensitize cells to apoptotic cell death"],"prefix":"10.1242","volume":"138","author":[{"given":"Mariana","family":"Joaquim","sequence":"first","affiliation":[{"name":"University of Cologne 1 Institute for Genetics , , 50674 Cologne ,","place":["Germany"]},{"name":"University of Cologne 2 Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) , , 50931 Cologne ,","place":["Germany"]},{"name":"University of Cologne 3 Center for Molecular Medicine Cologne (CMMC) , , 50931 Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Bianca","family":"Bulimaga","sequence":"additional","affiliation":[{"name":"University of Cologne 1 Institute for Genetics , , 50674 Cologne ,","place":["Germany"]},{"name":"University of Cologne 2 Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) , , 50931 Cologne ,","place":["Germany"]},{"name":"University of Cologne 3 Center for Molecular Medicine Cologne (CMMC) , , 50931 Cologne ,","place":["Germany"]},{"name":"University of Cologne 4 Institute of Pathology, Medical Faculty and University Hospital , , 50937 Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie A.","family":"Mohn","sequence":"additional","affiliation":[{"name":"University of Cologne 1 Institute for Genetics , , 50674 Cologne ,","place":["Germany"]},{"name":"University of Cologne 2 Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) , , 50931 Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solenn","family":"Plouzennec","sequence":"additional","affiliation":[{"name":"University of Angers 5 , MitoLab Team, MitoVasc Unit, CNRS UMR6015, INSERM U1083, Structure F\u00e9d\u00e9rative de Recherche (SFR), Interactions Cellulaires et Applications Th\u00e9rapeutiques (ICAT), 49330, Angers ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon","family":"Osinski","sequence":"additional","affiliation":[{"name":"University of Cologne 1 Institute for Genetics , , 50674 Cologne ,","place":["Germany"]},{"name":"University of Cologne 2 Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) , , 50931 Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selver","family":"Altin","sequence":"additional","affiliation":[{"name":"University of Cologne 1 Institute for Genetics , , 50674 Cologne ,","place":["Germany"]},{"name":"University of Cologne 2 Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) , , 50931 Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Mahabir","sequence":"additional","affiliation":[{"name":"University of Cologne 6 Comparative Medicine, Center for Molecular Medicine Cologne (CMMC), Medical Faculty and University Hospital , , 50931 Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Chevrollier","sequence":"additional","affiliation":[{"name":"University of Angers 5 , MitoLab Team, MitoVasc Unit, CNRS UMR6015, INSERM U1083, Structure F\u00e9d\u00e9rative de Recherche (SFR), Interactions Cellulaires et Applications Th\u00e9rapeutiques (ICAT), 49330, Angers ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0879-3119","authenticated-orcid":false,"given":"Mafalda","family":"Escobar-Henriques","sequence":"additional","affiliation":[{"name":"University of Cologne 1 Institute for Genetics , , 50674 Cologne ,","place":["Germany"]},{"name":"University of Cologne 2 Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) , , 50931 Cologne ,","place":["Germany"]},{"name":"University of Cologne 3 Center for Molecular Medicine Cologne (CMMC) , , 50931 Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2025,9,25]]},"reference":[{"key":"2025092505584129200_JCS263691C1","doi-asserted-by":"publisher","first-page":"6181","DOI":"10.1038\/s41598-022-10220-0","article-title":"Clinical and genetic features of a cohort of patients with MFN2-related neuropathy","volume":"12","author":"Abati","year":"2022","journal-title":"Sci. Rep."},{"key":"2025092505584129200_JCS263691C2","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.expneurol.2008.01.010","article-title":"Mitochondrial fusion and function in Charcot-Marie-Tooth type 2A patient fibroblasts with mitofusin 2 mutations","volume":"211","author":"Amiott","year":"2008","journal-title":"Exp. Neurol."},{"key":"2025092505584129200_JCS263691C3","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1083\/jcb.201308006","article-title":"The i-AAA protease YME1L and OMA1 cleave OPA1 to balance mitochondrial fusion and fission","volume":"204","author":"Anand","year":"2014","journal-title":"J. Cell Biol."},{"key":"2025092505584129200_JCS263691C4","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1111\/jns.12228","article-title":"Clinical and genetic diversities of Charcot-Marie-Tooth disease with MFN2 mutations in a large case study","volume":"22","author":"Ando","year":"2017","journal-title":"J. Peripher. Nerv. Syst."},{"key":"2025092505584129200_JCS263691C5","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/j.molcel.2012.12.003","article-title":"Two deubiquitylases act on mitofusin and regulate mitochondrial fusion along independent pathways","volume":"49","author":"Anton","year":"2013","journal-title":"Mol. Cell"},{"key":"2025092505584129200_JCS263691C6","doi-asserted-by":"publisher","first-page":"e201900491","DOI":"10.26508\/lsa.201900491","article-title":"Plasticity in salt bridge allows fusion-competent ubiquitylation of mitofusins and Cdc48 recognition","volume":"2","author":"Anton","year":"2019","journal-title":"Life Sci. Alliance"},{"key":"2025092505584129200_JCS263691C92","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0169999","article-title":"The effect of a novel c.820C&gt;T (Arg274Trp) mutation in the mitofusin 2 gene on fibroblast metabolism and clinical manifestation in a patient","volume":"12","author":"Ber\u0119sewicz","year":"2017","journal-title":"PloS One"},{"key":"2025092505584129200_JCS263691C7","doi-asserted-by":"publisher","first-page":"16900","DOI":"10.1038\/s41598-018-35133-9","article-title":"Molecular modelling of mitofusin 2 for a prediction for Charcot-Marie-Tooth 2A clinical severity","volume":"8","author":"Ber\u0119sewicz","year":"2018","journal-title":"Sci. Rep."},{"key":"2025092505584129200_JCS263691C8","doi-asserted-by":"publisher","first-page":"2328","DOI":"10.1073\/pnas.1810932116","article-title":"Altered interplay between endoplasmic reticulum and mitochondria in Charcot-Marie-Tooth type 2A neuropathy","volume":"116","author":"Bernard-Marissal","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025092505584129200_JCS263691C9","article-title":"Charcot-Marie-tooth hereditary neuropathy overview","volume-title":"GeneReviews((R))","author":"Bird","year":"1993"},{"key":"2025092505584129200_JCS263691C10","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1111\/jns.12539","article-title":"Recent advances in the treatment of Charcot-Marie-Tooth neuropathies","volume":"28","author":"Bolino","year":"2023","journal-title":"J. Peripher. Nerv. Syst."},{"key":"2025092505584129200_JCS263691C11","doi-asserted-by":"publisher","first-page":"11649","DOI":"10.1073\/pnas.0703976104","article-title":"Bak regulates mitochondrial morphology and pathology during apoptosis by interacting with mitofusins","volume":"104","author":"Brooks","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025092505584129200_JCS263691C12","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/1478-811X-8-31","article-title":"PARP-1 cleavage fragments: signatures of cell-death proteases in neurodegeneration","volume":"8","author":"Chaitanya","year":"2010","journal-title":"Cell Commun. Signal"},{"key":"2025092505584129200_JCS263691C13","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1083\/jcb.200211046","article-title":"Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development","volume":"160","author":"Chen","year":"2003","journal-title":"J. Cell Biol."},{"key":"2025092505584129200_JCS263691C14","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1016\/j.cell.2007.06.026","article-title":"Mitochondrial fusion protects against neurodegeneration in the cerebellum","volume":"130","author":"Chen","year":"2007","journal-title":"Cell"},{"key":"2025092505584129200_JCS263691C15","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1016\/j.stemcr.2020.03.024","article-title":"MFN2 plays a distinct role from MFN1 in regulating spermatogonial differentiation","volume":"14","author":"Chen","year":"2020","journal-title":"Stem Cell Rep."},{"key":"2025092505584129200_JCS263691C16","doi-asserted-by":"publisher","first-page":"1767","DOI":"10.3892\/ijo.2014.2343","article-title":"Mitofusin 1 degradation is induced by a disruptor of mitochondrial calcium homeostasis, CGP37157: a role in apoptosis in prostate cancer cells","volume":"44","author":"Choudhary","year":"2014","journal-title":"Int. J. Oncol."},{"key":"2025092505584129200_JCS263691C17","doi-asserted-by":"publisher","first-page":"jcs257808","DOI":"10.1242\/jcs.257808","article-title":"MITOL-mediated DRP1 ubiquitylation and degradation promotes mitochondrial hyperfusion in a CMT2A-linked MFN2 mutant","volume":"135","author":"Das","year":"2022","journal-title":"J. Cell Sci."},{"key":"2025092505584129200_JCS263691C18","doi-asserted-by":"publisher","first-page":"101825","DOI":"10.1016\/j.mito.2023.101825","article-title":"CMT2A-linked MFN2 mutation, T206I promotes mitochondrial hyperfusion and predisposes cells towards mitophagy","volume":"74","author":"Das","year":"2024","journal-title":"Mitochondrion"},{"key":"2025092505584129200_JCS263691C19","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1002\/bip.22855","article-title":"Invited review: mechanisms of GTP hydrolysis and conformational transitions in the dynamin superfamily","volume":"105","author":"Daumke","year":"2016","journal-title":"Biopolymers"},{"key":"2025092505584129200_JCS263691C20","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1083\/jcb.200611080","article-title":"Complementation between mouse Mfn1 and Mfn2 protects mitochondrial fusion defects caused by CMT2A disease mutations","volume":"176","author":"Detmer","year":"2007","journal-title":"J. Cell Biol."},{"key":"2025092505584129200_JCS263691C21","doi-asserted-by":"publisher","first-page":"517","DOI":"10.3389\/fphys.2019.00517","article-title":"Mitofusins: disease gatekeepers and hubs in mitochondrial quality control by E3 ligases","volume":"10","author":"Escobar-Henriques","year":"2019","journal-title":"Front. Physiol."},{"key":"2025092505584129200_JCS263691C22","doi-asserted-by":"publisher","first-page":"1690","DOI":"10.1212\/WNL.0b013e31821a441e","article-title":"MFN2 mutations cause severe phenotypes in most patients with CMT2A","volume":"76","author":"Feely","year":"2011","journal-title":"Neurology"},{"key":"2025092505584129200_JCS263691C23","doi-asserted-by":"publisher","first-page":"e61119","DOI":"10.7554\/eLife.61119","article-title":"Burst mitofusin activation reverses neuromuscular dysfunction in murine CMT2A","volume":"9","author":"Franco","year":"2020","journal-title":"eLife"},{"key":"2025092505584129200_JCS263691C24","doi-asserted-by":"publisher","first-page":"2110","DOI":"10.3390\/life12122110","article-title":"Mitochondria clumping vs. mitochondria fusion in CMT2A diseases","volume":"12","author":"Franco","year":"2022","journal-title":"Life"},{"key":"2025092505584129200_JCS263691C25","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1016\/S1534-5807(01)00055-7","article-title":"The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis","volume":"1","author":"Frank","year":"2001","journal-title":"Dev. Cell"},{"key":"2025092505584129200_JCS263691C26","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1038\/sj.onc.1202065","article-title":"Acceleration of apoptotic cell death after the cleavage of Bcl-XL protein by caspase-3-like proteases","volume":"17","author":"Fujita","year":"1998","journal-title":"Oncogene"},{"key":"2025092505584129200_JCS263691C27","doi-asserted-by":"publisher","first-page":"8368","DOI":"10.1038\/s41467-023-44033-0","article-title":"NEMO reshapes the alpha-Synuclein aggregate interface and acts as an autophagy adapter by co-condensation with p62","volume":"14","author":"Furthmann","year":"2023","journal-title":"Nat. Commun."},{"key":"2025092505584129200_JCS263691C28","doi-asserted-by":"publisher","first-page":"116","DOI":"10.3390\/cells9010116","article-title":"Mfn2 ablation in the adult mouse hippocampus and cortex causes neuronal death","volume":"9","author":"Han","year":"2020","journal-title":"Cells"},{"key":"2025092505584129200_JCS263691C29","doi-asserted-by":"publisher","first-page":"1756","DOI":"10.1523\/JNEUROSCI.2324-19.2020","article-title":"Neuronal mitochondria modulation of LPS-induced neuroinflammation","volume":"40","author":"Harland","year":"2020","journal-title":"J. Neurosci."},{"key":"2025092505584129200_JCS263691C30","doi-asserted-by":"publisher","first-page":"3153","DOI":"10.1242\/jcs.02449","article-title":"Mutational analysis of action of mitochondrial fusion factor mitofusin-2","volume":"118","author":"Honda","year":"2005","journal-title":"J. Cell Sci."},{"key":"2025092505584129200_JCS263691C31","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.molcel.2010.11.030","article-title":"The soluble form of Bax regulates mitochondrial fusion via MFN2 homotypic complexes","volume":"41","author":"Hoppins","year":"2011","journal-title":"Mol. Cell"},{"key":"2025092505584129200_JCS263691C32","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.ejcb.2007.04.002","article-title":"Mitochondrial clustering induced by overexpression of the mitochondrial fusion protein Mfn2 causes mitochondrial dysfunction and cell death","volume":"86","author":"Huang","year":"2007","journal-title":"Eur. J. Cell Biol."},{"key":"2025092505584129200_JCS263691C33","doi-asserted-by":"publisher","first-page":"e108587","DOI":"10.15252\/embj.2021108587","article-title":"DRP1 interacts directly with BAX to induce its activation and apoptosis","volume":"41","author":"Jenner","year":"2022","journal-title":"EMBO J."},{"key":"2025092505584129200_JCS263691C34","doi-asserted-by":"publisher","first-page":"S373","DOI":"10.1007\/s12032-010-9662-5","article-title":"Anti-tumour efficacy of mitofusin-2 in urinary bladder carcinoma","volume":"28","author":"Jin","year":"2011","journal-title":"Med. Oncol."},{"key":"2025092505584129200_JCS263691C35","doi-asserted-by":"publisher","first-page":"572182","DOI":"10.3389\/fcell.2020.572182","article-title":"Role of mitofusins and mitophagy in life or death decisions","volume":"8","author":"Joaquim","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"2025092505584129200_JCS263691C36","doi-asserted-by":"publisher","first-page":"1501","DOI":"10.1038\/s41467-025-56673-5","article-title":"Mitofusin 2 displays fusion-independent roles in proteostasis surveillance","volume":"16","author":"Joaquim","year":"2025","journal-title":"Nat. Commun."},{"key":"2025092505584129200_JCS263691C37","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1083\/jcb.200209124","article-title":"Spatial and temporal association of Bax with mitochondrial fission sites, Drp1, and Mfn2 during apoptosis","volume":"159","author":"Karbowski","year":"2002","journal-title":"J. Cell Biol."},{"key":"2025092505584129200_JCS263691C38","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1038\/nature05111","article-title":"Role of Bax and Bak in mitochondrial morphogenesis","volume":"443","author":"Karbowski","year":"2006","journal-title":"Nature"},{"key":"2025092505584129200_JCS263691C39","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/s00439-004-1199-2","article-title":"Mitochondrial GTPase mitofusin 2 mutation in Charcot-Marie-Tooth neuropathy type 2A","volume":"116","author":"Kijima","year":"2005","journal-title":"Hum. Genet."},{"key":"2025092505584129200_JCS263691C40","doi-asserted-by":"publisher","DOI":"10.1101\/2023.03.15.532838","article-title":"MFN2-dependent recruitment of ATAT1 coordinates mitochondria motility with alpha-tubulin acetylation and is disrupted in CMT2A","author":"Kumar","year":"2023","journal-title":"bioRxiv"},{"key":"2025092505584129200_JCS263691C41","doi-asserted-by":"publisher","first-page":"1782","DOI":"10.1093\/hmg\/ddz008","article-title":"MFN2 mutations in Charcot-Marie-Tooth disease alter mitochondria-associated ER membrane function but do not impair bioenergetics","volume":"28","author":"Larrea","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"2025092505584129200_JCS263691C42","doi-asserted-by":"publisher","first-page":"5001","DOI":"10.1091\/mbc.e04-04-0294","article-title":"Roles of the mammalian mitochondrial fission and fusion mediators Fis1, Drp1, and Opa1 in apoptosis","volume":"15","author":"Lee","year":"2004","journal-title":"Mol. Biol. Cell"},{"key":"2025092505584129200_JCS263691C43","doi-asserted-by":"publisher","first-page":"4343","DOI":"10.1091\/mbc.e02-06-0330","article-title":"Mitochondrial fusion in human cells is efficient, requires the inner membrane potential, and is mediated by mitofusins","volume":"13","author":"Legros","year":"2002","journal-title":"Mol. Biol. Cell"},{"key":"2025092505584129200_JCS263691C44","doi-asserted-by":"publisher","first-page":"4914","DOI":"10.1038\/s41467-019-12912-0","article-title":"Structural insights of human mitofusin-2 into mitochondrial fusion and CMT2A onset","volume":"10","author":"Li","year":"2019","journal-title":"Nat. Commun."},{"key":"2025092505584129200_JCS263691C45","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/S0014-5793(01)02693-X","article-title":"The protonophore CCCP induces mitochondrial permeability transition without cytochrome c release in human osteosarcoma cells","volume":"503","author":"Lim","year":"2001","journal-title":"FEBS Lett."},{"key":"2025092505584129200_JCS263691C46","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s12964-019-0499-z","article-title":"Cell death induced by the ER stressor thapsigargin involves death receptor 5, a non-autophagic function of MAP1LC3B, and distinct contributions from unfolded protein response components","volume":"18","author":"Lindner","year":"2020","journal-title":"Cell Commun. Signal."},{"key":"2025092505584129200_JCS263691C47","doi-asserted-by":"publisher","first-page":"10666","DOI":"10.1073\/pnas.1611481113","article-title":"Actinomycin D enhances killing of cancer cells by immunotoxin RG7787 through activation of the extrinsic pathway of apoptosis","volume":"113","author":"Liu","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025092505584129200_JCS263691C94","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"2025092505584129200_JCS263691C48","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1002\/ana.21086","article-title":"Mitochondrial coupling defect in Charcot-Marie-Tooth type 2A disease","volume":"61","author":"Loiseau","year":"2007","journal-title":"Ann. Neurol."},{"key":"2025092505584129200_JCS263691C95","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1016\/j.cell.2009.11.003","article-title":"Structure of a bacterial dynamin-like protein lipid tube provides a mechanism for assembly and membrane curving","volume":"139","author":"Low","year":"2009","journal-title":"Cell"},{"key":"2025092505584129200_JCS263691C49","first-page":"1904","article-title":"Actinomycin D inhibits cell proliferations and promotes apoptosis in osteosarcoma cells","volume":"8","author":"Lu","year":"2015","journal-title":"Int. J. Clin. Exp. Med."},{"key":"2025092505584129200_JCS263691C50","doi-asserted-by":"publisher","first-page":"2388","DOI":"10.15252\/embj.201488327","article-title":"Mfn2 downregulation in excitotoxicity causes mitochondrial dysfunction and delayed neuronal death","volume":"33","author":"Martorell-Riera","year":"2014","journal-title":"EMBO J."},{"key":"2025092505584129200_JCS263691C51","doi-asserted-by":"publisher","first-page":"4232","DOI":"10.1523\/JNEUROSCI.6248-09.2010","article-title":"Mitofusin 2 is necessary for transport of axonal mitochondria and interacts with the Miro\/Milton complex","volume":"30","author":"Misko","year":"2010","journal-title":"J. Neurosci."},{"key":"2025092505584129200_JCS263691C52","doi-asserted-by":"publisher","first-page":"4145","DOI":"10.1523\/JNEUROSCI.6338-11.2012","article-title":"Mitofusin2 mutations disrupt axonal mitochondrial positioning and promote axon degeneration","volume":"32","author":"Misko","year":"2012","journal-title":"J. Neurosci."},{"key":"2025092505584129200_JCS263691C53","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1016\/j.cell.2010.08.017","article-title":"Membrane remodeling induced by the dynamin-related protein Drp1 stimulates Bax oligomerization","volume":"142","author":"Montessuit","year":"2010","journal-title":"Cell"},{"key":"2025092505584129200_JCS263691C54","doi-asserted-by":"publisher","first-page":"eaba8271","DOI":"10.1126\/sciadv.aba8271","article-title":"Neuronal metabolic rewiring promotes resilience to neurodegeneration caused by mitochondrial dysfunction","volume":"6","author":"Motori","year":"2020","journal-title":"Sci. Adv."},{"key":"2025092505584129200_JCS263691C55","doi-asserted-by":"publisher","first-page":"e105074","DOI":"10.15252\/embj.2020105074","article-title":"Mitochondrial Safeguard: a stress response that offsets extreme fusion and protects respiratory function via flickering-induced Oma1 activation","volume":"39","author":"Murata","year":"2020","journal-title":"EMBO J."},{"key":"2025092505584129200_JCS263691C56","doi-asserted-by":"publisher","first-page":"25060","DOI":"10.1074\/jbc.M501599200","article-title":"Activated mitofusin 2 signals mitochondrial fusion, interferes with Bax activation, and reduces susceptibility to radical induced depolarization","volume":"280","author":"Neuspiel","year":"2005","journal-title":"J. Biol. Chem."},{"key":"2025092505584129200_JCS263691C57","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/B978-0-12-385114-7.00004-0","article-title":"Measuring ER stress and the unfolded protein response using mammalian tissue culture system","volume":"490","author":"Oslowski","year":"2011","journal-title":"Methods Enzymol."},{"key":"2025092505584129200_JCS263691C58","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1128\/MCB.00911-10","article-title":"Mitofusin-2 maintains mitochondrial structure and contributes to stress-induced permeability transition in cardiac myocytes","volume":"31","author":"Papanicolaou","year":"2011","journal-title":"Mol. Cell. Biol."},{"key":"2025092505584129200_JCS263691C59","doi-asserted-by":"publisher","first-page":"H167","DOI":"10.1152\/ajpheart.00833.2011","article-title":"Cardiomyocyte deletion of mitofusin-1 leads to mitochondrial fragmentation and improves tolerance to ROS-induced mitochondrial dysfunction and cell death","volume":"302","author":"Papanicolaou","year":"2012","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"2025092505584129200_JCS263691C60","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1038\/s41582-019-0254-5","article-title":"Next-generation sequencing in Charcot-Marie-Tooth disease: opportunities and challenges","volume":"15","author":"Pipis","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"2025092505584129200_JCS263691C61","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1016\/j.molcel.2023.02.012","article-title":"Determinants and outcomes of mitochondrial dynamics","volume":"83","author":"Quintana-Cabrera","year":"2023","journal-title":"Mol. Cell"},{"key":"2025092505584129200_JCS263691C62","doi-asserted-by":"publisher","first-page":"21836","DOI":"10.1074\/jbc.M202726200","article-title":"Coupling endoplasmic reticulum stress to the cell death program. An Apaf-1-independent intrinsic pathway","volume":"277","author":"Rao","year":"2002","journal-title":"J. Biol. Chem."},{"key":"2025092505584129200_JCS263691C63","doi-asserted-by":"publisher","first-page":"2342","DOI":"10.47391\/JPMA.063","article-title":"Analysis of the conformational changes caused by the mutations in mitofusin2 gene by Insilico approach","volume":"70","author":"Rasheed","year":"2020","journal-title":"J. Pak. Med. Assoc."},{"key":"2025092505584129200_JCS263691C64","doi-asserted-by":"publisher","first-page":"4266","DOI":"10.1093\/hmg\/ddw258","article-title":"Selective mitochondrial depletion, apoptosis resistance, and increased mitophagy in human Charcot-Marie-Tooth 2A motor neurons","volume":"25","author":"Rizzo","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"2025092505584129200_JCS263691C65","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1126\/science.aao1785","article-title":"MFN2 agonists reverse mitochondrial defects in preclinical models of Charcot-Marie-Tooth disease type 2A","volume":"360","author":"Rocha","year":"2018","journal-title":"Science"},{"key":"2025092505584129200_JCS263691C66","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1093\/brain\/awr323","article-title":"The MFN2 gene is responsible for mitochondrial DNA instability and optic atrophy \u2018plus\u2019 phenotype","volume":"135","author":"Rouzier","year":"2012","journal-title":"Brain"},{"key":"2025092505584129200_JCS263691C67","doi-asserted-by":"publisher","first-page":"e201900527","DOI":"10.26508\/lsa.201900527","article-title":"Defective nucleotide-dependent assembly and membrane fusion in Mfn2 CMT2A variants improved by Bax","volume":"3","author":"Samanas","year":"2020","journal-title":"Life Sci. Alliance"},{"key":"2025092505584129200_JCS263691C68","doi-asserted-by":"publisher","first-page":"2177","DOI":"10.1093\/brain\/124.11.2177","article-title":"Regulation of Schwann cell proliferation and apoptosis in PMP22-deficient mice and mouse models of Charcot-Marie-Tooth disease type 1A","volume":"124","author":"Sancho","year":"2001","journal-title":"Brain"},{"key":"2025092505584129200_JCS263691C69","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.expneurol.2014.10.005","article-title":"Axonal Charcot-Marie-Tooth disease patient-derived motor neurons demonstrate disease-specific phenotypes including abnormal electrophysiological properties","volume":"263","author":"Saporta","year":"2015","journal-title":"Exp. Neurol."},{"key":"2025092505584129200_JCS263691C70","doi-asserted-by":"publisher","first-page":"5109","DOI":"10.1093\/hmg\/ddv229","article-title":"Homozygous mutations in MFN2 cause multiple symmetric lipomatosis associated with neuropathy","volume":"24","author":"Sawyer","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"2025092505584129200_JCS263691C71","doi-asserted-by":"publisher","first-page":"606","DOI":"10.12688\/f1000research.53230.2","article-title":"Characterization of a novel variant in the HR1 domain of MFN2 in a patient with ataxia, optic atrophy and sensorineural hearing loss","volume":"10","author":"Sharma","year":"2021","journal-title":"F1000Res."},{"key":"2025092505584129200_JCS263691C72","doi-asserted-by":"publisher","first-page":"e00498","DOI":"10.7554\/eLife.00498","article-title":"Pharmacological brake-release of mRNA translation enhances cognitive memory","volume":"2","author":"Sidrauski","year":"2013","journal-title":"eLife"},{"key":"2025092505584129200_JCS263691C73","doi-asserted-by":"publisher","first-page":"e30015","DOI":"10.7554\/eLife.30015","article-title":"Cdc48 regulates a deubiquitylase cascade critical for mitochondrial fusion","volume":"7","author":"Simoes","year":"2018","journal-title":"eLife"},{"key":"2025092505584129200_JCS263691C74","doi-asserted-by":"publisher","first-page":"e202101305","DOI":"10.26508\/lsa.202101305","article-title":"A dominant negative mitofusin causes mitochondrial perinuclear clusters because of aberrant tethering","volume":"6","author":"Sloat","year":"2023","journal-title":"Life Sci. Alliance"},{"key":"2025092505584129200_JCS263691C75","doi-asserted-by":"publisher","first-page":"11569","DOI":"10.3390\/ijms222111569","article-title":"Aberrant mitochondrial dynamics and exacerbated response to neuroinflammation in a novel mouse model of CMT2A","volume":"22","author":"Stavropoulos","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"2025092505584129200_JCS263691C96","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1111\/jns.12564","article-title":"Mitofusin 1 overexpression rescues the abnormal mitochondrial dynamics caused by the Mitofusin 2 K357T mutation in vitro","volume":"28","author":"Stavropoulos","year":"2023","journal-title":"J. Periph. Nerv. Syst."},{"key":"2025092505584129200_JCS263691C76","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1016\/j.neurol.2016.06.007","article-title":"Hereditary neuropathies: an update","volume":"172","author":"Stojkovic","year":"2016","journal-title":"Rev. Neurol. (Paris)"},{"key":"2025092505584129200_JCS263691C77","doi-asserted-by":"publisher","first-page":"52726","DOI":"10.1074\/jbc.M408910200","article-title":"Fzo1, a protein involved in mitochondrial fusion, inhibits apoptosis","volume":"279","author":"Sugioka","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2025092505584129200_JCS263691C78","doi-asserted-by":"publisher","first-page":"e179570","DOI":"10.1172\/JCI179570","article-title":"Targeting apoptotic pathways for cancer therapy","volume":"134","author":"Tian","year":"2024","journal-title":"J. Clin. Invest."},{"key":"2025092505584129200_JCS263691C79","doi-asserted-by":"publisher","first-page":"109824","DOI":"10.1016\/j.envres.2020.109824","article-title":"Ferroptosis mediated by the interaction between Mfn2 and IREalpha promotes arsenic-induced nonalcoholic steatohepatitis","volume":"188","author":"Wei","year":"2020","journal-title":"Environ. Res."},{"key":"2025092505584129200_JCS263691C80","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.3390\/cells8101289","article-title":"The Charcot-Marie Tooth disease mutation R94Q in MFN2 decreases ATP production but increases mitochondrial respiration under conditions of mild oxidative stress","volume":"8","author":"Wolf","year":"2019","journal-title":"Cells"},{"key":"2025092505584129200_JCS263691C81","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1158\/1535-7163.MCT-07-0382","article-title":"Adenovirus-expressed human hyperplasia suppressor gene induces apoptosis in cancer cells","volume":"7","author":"Wu","year":"2008","journal-title":"Mol. Cancer Ther."},{"key":"2025092505584129200_JCS263691C82","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1248\/bpb.b17-00672","article-title":"Bavachin induces apoptosis through mitochondrial regulated ER stress pathway in HepG2 cells","volume":"41","author":"Yang","year":"2018","journal-title":"Biol. Pharm. Bull."},{"key":"2025092505584129200_JCS263691C83","doi-asserted-by":"publisher","first-page":"3680","DOI":"10.3892\/etm.2018.6595","article-title":"MFN2 ameliorates cell apoptosis in a cellular model of Parkinson's disease induced by rotenone","volume":"16","author":"Yang","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"2025092505584129200_JCS263691C84","doi-asserted-by":"publisher","first-page":"3775","DOI":"10.1038\/s41467-022-31324-1","article-title":"Modulating mitofusins to control mitochondrial function and signaling","volume":"13","author":"Zacharioudakis","year":"2022","journal-title":"Nat. Commun."},{"key":"2025092505584129200_JCS263691C85","doi-asserted-by":"publisher","first-page":"858286","DOI":"10.3389\/fcell.2022.858286","article-title":"The role of impaired mitochondrial dynamics in MFN2-mediated pathology","volume":"10","author":"Zaman","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"2025092505584129200_JCS263691C86","doi-asserted-by":"publisher","first-page":"e49158","DOI":"10.7554\/eLife.49158","article-title":"Neuronal TORC1 modulates longevity via AMPK and cell nonautonomous regulation of mitochondrial dynamics in C. elegans","volume":"8","author":"Zhang","year":"2019","journal-title":"eLife"},{"key":"2025092505584129200_JCS263691C87","doi-asserted-by":"publisher","first-page":"134673","DOI":"10.1016\/j.ijbiomac.2024.134673","article-title":"Mfn2(R364W), Mfn2(G176S), and Mfn2(H165R) mutations drive Charcot-Marie-Tooth type 2A disease by inducing apoptosis and mitochondrial oxidative phosphorylation damage","volume":"278","author":"Zhang","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"2025092505584129200_JCS263691C88","doi-asserted-by":"publisher","first-page":"e0125680","DOI":"10.1371\/journal.pone.0125680","article-title":"Mfn2 affects embryo development via mitochondrial dysfunction and apoptosis","volume":"10","author":"Zhao","year":"2015","journal-title":"PLoS ONE"},{"key":"2025092505584129200_JCS263691C89","doi-asserted-by":"publisher","first-page":"1756","DOI":"10.1172\/JCI124194","article-title":"Restoring mitofusin balance prevents axonal degeneration in a Charcot-Marie-Tooth type 2A model","volume":"129","author":"Zhou","year":"2019","journal-title":"J. Clin. Invest."},{"key":"2025092505584129200_JCS263691C90","doi-asserted-by":"publisher","first-page":"1137151","DOI":"10.3389\/fphar.2023.1137151","article-title":"Human PARP1 substrates and regulators of its catalytic activity: an updated overview","volume":"14","author":"Zhu","year":"2023","journal-title":"Front. Pharmacol."},{"key":"2025092505584129200_JCS263691C91","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1038\/ng1514","article-title":"Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease","volume":"37","author":"Zuchner","year":"2005","journal-title":"Nat. Genet."}],"container-title":["Journal of Cell Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/jcs\/article-pdf\/doi\/10.1242\/jcs.263691\/3666509\/jcs263691.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/jcs\/article-pdf\/doi\/10.1242\/jcs.263691\/3666509\/jcs263691.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T09:59:07Z","timestamp":1758794347000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/jcs\/article\/138\/18\/jcs263691\/369280\/Charcot-Marie-Tooth-type-2A-variants-of-mitofusin"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,15]]},"references-count":95,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2025,9,15]]}},"URL":"https:\/\/doi.org\/10.1242\/jcs.263691","relation":{},"ISSN":["0021-9533","1477-9137"],"issn-type":[{"value":"0021-9533","type":"print"},{"value":"1477-9137","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,15]]},"article-number":"jcs263691"}}