{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:12:32Z","timestamp":1790745152489,"version":"4.1.0"},"reference-count":44,"publisher":"Rockefeller University Press","issue":"3","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,2,3]]},"abstract":"<jats:p>Ablation of the mitochondrial fusion and endoplasmic reticulum (ER)\u2013tethering protein Mfn2 causes ER stress, but whether this is just an epiphenomenon of mitochondrial dysfunction or a contributor to the phenotypes in mitofusin (Mfn)-depleted Drosophila melanogaster is unclear. In this paper, we show that reduction of ER dysfunction ameliorates the functional and developmental defects of flies lacking the single Mfn mitochondrial assembly regulatory factor (Marf). Ubiquitous or neuron- and muscle-specific Marf ablation was lethal, altering mitochondrial and ER morphology and triggering ER stress that was conversely absent in flies lacking the fusion protein optic atrophy 1. Expression of Mfn2 and ER stress reduction in flies lacking Marf corrected ER shape, attenuating the developmental and motor defects. Thus, ER stress is a targetable pathogenetic component of the phenotypes caused by Drosophila Mfn ablation.<\/jats:p>","DOI":"10.1083\/jcb.201306121","type":"journal-article","created":{"date-parts":[[2014,1,28]],"date-time":"2014-01-28T04:41:17Z","timestamp":1390884077000},"page":"303-312","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":63,"title":["Reduction of endoplasmic reticulum stress attenuates the defects caused by <i>Drosophila<\/i> mitofusin depletion"],"prefix":"10.1083","volume":"204","author":[{"given":"Valentina","family":"Debattisti","sequence":"first","affiliation":[{"name":"Dulbecco Telethon Institute, Venetian Institute of Molecular Medicine, 35129 Padua, Italy 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Pendin","sequence":"additional","affiliation":[{"name":"Eugenio Medea Scientific Institute, 31015 Conegliano, Italy 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Ziviani","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology and Metabolism, University of Geneva, 1205 Geneva, Switzerland 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Daga","sequence":"additional","affiliation":[{"name":"Eugenio Medea Scientific Institute, 31015 Conegliano, Italy 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Scorrano","sequence":"additional","affiliation":[{"name":"Dulbecco Telethon Institute, Venetian Institute of Molecular Medicine, 35129 Padua, Italy 1"},{"name":"Department of Biology, University of Padua, 35121 Padua, Italy 4"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2014,1,27]]},"reference":[{"key":"2023072306244871100_bib1","doi-asserted-by":"publisher","first-page":"4106","DOI":"10.1038\/emboj.2012.202","article-title":"Upregulated function of mitochondria-associated ER membranes in Alzheimer disease","volume":"31","author":"Area-Gomez","year":"2012","journal-title":"EMBO J."},{"key":"2023072306244871100_bib2","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1242\/dev.118.2.401","article-title":"Targeted gene expression as a means of altering cell fates and generating dominant phenotypes","volume":"118","author":"Brand","year":"1993","journal-title":"Development."},{"key":"2023072306244871100_bib3","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1093\/brain\/awq082","article-title":"Expression of mitofusin 2(R94Q) in a transgenic mouse leads to Charcot-Marie-Tooth neuropathy type 2A","volume":"133","author":"Cartoni","year":"2010","journal-title":"Brain."},{"key":"2023072306244871100_bib4","doi-asserted-by":"publisher","first-page":"2144","DOI":"10.1093\/hmg\/ddr100","article-title":"The ER stress factor XBP1s prevents amyloid-beta neurotoxicity","volume":"20","author":"Casas-Tinto","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"2023072306244871100_bib5","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1038\/embor.2010.151","article-title":"Trichoplein\/mitostatin regulates endoplasmic reticulum-mitochondria juxtaposition","volume":"11","author":"Cerqua","year":"2010","journal-title":"EMBO Rep."},{"key":"2023072306244871100_bib6","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":"2023072306244871100_bib7","doi-asserted-by":"publisher","first-page":"26185","DOI":"10.1074\/jbc.M503062200","article-title":"Disruption of fusion results in mitochondrial heterogeneity and dysfunction","volume":"280","author":"Chen","year":"2005","journal-title":"J. Biol. Chem."},{"key":"2023072306244871100_bib8","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1161\/CIRCRESAHA.112.266585","article-title":"Mitofusin 2-containing mitochondrial-reticular microdomains direct rapid cardiomyocyte bioenergetic responses via interorganelle Ca(2+) crosstalk","volume":"111","author":"Chen","year":"2012","journal-title":"Circ. Res."},{"key":"2023072306244871100_bib9","doi-asserted-by":"publisher","first-page":"15927","DOI":"10.1073\/pnas.0407043101","article-title":"OPA1 requires mitofusin 1 to promote mitochondrial fusion","volume":"101","author":"Cipolat","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072306244871100_bib10","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1038\/nature07534","article-title":"Mitofusin 2 tethers endoplasmic reticulum to mitochondria","volume":"456","author":"de Brito","year":"2008","journal-title":"Nature."},{"key":"2023072306244871100_bib11","doi-asserted-by":"publisher","first-page":"2715","DOI":"10.1038\/emboj.2010.177","article-title":"An intimate liaison: spatial organization of the endoplasmic reticulum-mitochondria relationship","volume":"29","author":"de Brito","year":"2010","journal-title":"EMBO J."},{"key":"2023072306244871100_bib12","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":"2023072306244871100_bib13","doi-asserted-by":"publisher","first-page":"14503","DOI":"10.1073\/pnas.0803998105","article-title":"The Parkinson\u2019s disease genes pink1 and parkin promote mitochondrial fission and\/or inhibit fusion in Drosophila","volume":"105","author":"Deng","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072306244871100_bib14","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":"2023072306244871100_bib15","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1093\/hmg\/ddm314","article-title":"Hindlimb gait defects due to motor axon loss and reduced distal muscles in a transgenic mouse model of Charcot-Marie-Tooth type 2A","volume":"17","author":"Detmer","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"2023072306244871100_bib16","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1161\/CIRCRESAHA.110.236745","article-title":"MARF and Opa1 control mitochondrial and cardiac function in Drosophila","volume":"108","author":"Dorn","year":"2011","journal-title":"Circ. Res."},{"key":"2023072306244871100_bib17","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1126\/science.1207385","article-title":"ER tubules mark sites of mitochondrial division","volume":"334","author":"Friedman","year":"2011","journal-title":"Science."},{"key":"2023072306244871100_bib18","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/S0092-8674(00)80319-0","article-title":"Developmentally regulated mitochondrial fusion mediated by a conserved, novel, predicted GTPase","volume":"90","author":"Hales","year":"1997","journal-title":"Cell."},{"key":"2023072306244871100_bib19","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1038\/nature11910","article-title":"Autophagosomes form at ER-mitochondria contact sites","volume":"495","author":"Hamasaki","year":"2013","journal-title":"Nature."},{"key":"2023072306244871100_bib20","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/S0925-4773(02)00141-7","article-title":"Differential expression of the Drosophila mitofusin genes fuzzy onions (fzo) and dmfn","volume":"116","author":"Hwa","year":"2002","journal-title":"Mech. Dev."},{"key":"2023072306244871100_bib21","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.1111\/j.1471-4159.2006.04440.x","article-title":"Neurodegeneration of mouse nigrostriatal dopaminergic system induced by repeated oral administration of rotenone is prevented by 4-phenylbutyrate, a chemical chaperone","volume":"101","author":"Inden","year":"2007","journal-title":"J. Neurochem."},{"key":"2023072306244871100_bib22","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1038\/ng1270","article-title":"Mitochondrial dysfunction and apoptosis in myopathic mice with collagen VI deficiency","volume":"35","author":"Irwin","year":"2003","journal-title":"Nat. Genet."},{"key":"2023072306244871100_bib23","doi-asserted-by":"publisher","first-page":"6535","DOI":"10.1242\/jcs.01565","article-title":"Mitofusin 1 and 2 play distinct roles in mitochondrial fusion reactions via GTPase activity","volume":"117","author":"Ishihara","year":"2004","journal-title":"J. Cell Sci."},{"key":"2023072306244871100_bib24","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1093\/jb\/mvp052","article-title":"Gene expression profiling identifies a role for CHOP during inhibition of the mitochondrial respiratory chain","volume":"146","author":"Ishikawa","year":"2009","journal-title":"J. Biochem."},{"key":"2023072306244871100_bib25","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1126\/science.1241359","article-title":"Mitochondrial fusion directs cardiomyocyte differentiation via calcineurin and Notch signaling","volume":"342","author":"Kasahara","year":"2013","journal-title":"Science."},{"key":"2023072306244871100_bib26","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1126\/science.1175088","article-title":"An ER-mitochondria tethering complex revealed by a synthetic biology screen","volume":"325","author":"Kornmann","year":"2009","journal-title":"Science."},{"key":"2023072306244871100_bib27","doi-asserted-by":"publisher","first-page":"20321","DOI":"10.1074\/jbc.M112.359174","article-title":"Loss of mitofusin 2 promotes endoplasmic reticulum stress","volume":"287","author":"Ngoh","year":"2012","journal-title":"J. Biol. Chem."},{"key":"2023072306244871100_bib28","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/S0014-5793(02)02985-X","article-title":"The human dynamin-related protein OPA1 is anchored to the mitochondrial inner membrane facing the inter-membrane space","volume":"523","author":"Olichon","year":"2002","journal-title":"FEBS Lett."},{"key":"2023072306244871100_bib29","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1038\/nature08280","article-title":"Homotypic fusion of ER membranes requires the dynamin-like GTPase atlastin","volume":"460","author":"Orso","year":"2009","journal-title":"Nature."},{"key":"2023072306244871100_bib30","doi-asserted-by":"publisher","first-page":"12596","DOI":"10.1073\/pnas.221303298","article-title":"A conditional tissue-specific transgene expression system using inducible GAL4","volume":"98","author":"Osterwalder","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072306244871100_bib31","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1126\/science.1128294","article-title":"Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes","volume":"313","author":"Ozcan","year":"2006","journal-title":"Science."},{"key":"2023072306244871100_bib32","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":"2023072306244871100_bib33","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1006\/dbio.1996.9987","article-title":"Wingless signaling induces nautilus expression in the ventral mesoderm of the Drosophila embryo","volume":"176","author":"Ranganayakulu","year":"1996","journal-title":"Dev. Biol."},{"key":"2023072306244871100_bib34","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1038\/sj.emboj.7601477","article-title":"Unfolded protein response in a Drosophila model for retinal degeneration","volume":"26","author":"Ryoo","year":"2007","journal-title":"EMBO J."},{"key":"2023072306244871100_bib35","doi-asserted-by":"publisher","first-page":"e75774","DOI":"10.1371\/journal.pone.0075774","article-title":"Drosophila XBP1 expression reporter marks cells under endoplasmic reticulum stress and with high protein secretory load","volume":"8","author":"Ryoo","year":"2013","journal-title":"PLoS ONE."},{"key":"2023072306244871100_bib36","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1242\/jcs.114.5.867","article-title":"Control of mitochondrial morphology by a human mitofusin","volume":"114","author":"Santel","year":"2001","journal-title":"J. Cell Sci."},{"key":"2023072306244871100_bib37","doi-asserted-by":"publisher","first-page":"2763","DOI":"10.1242\/jcs.00479","article-title":"Mitofusin-1 protein is a generally expressed mediator of mitochondrial fusion in mammalian cells","volume":"116","author":"Santel","year":"2003","journal-title":"J. Cell Sci."},{"key":"2023072306244871100_bib38","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.cell.2013.09.003","article-title":"Mitofusin 2 in POMC neurons connects ER stress with leptin resistance and energy imbalance","volume":"155","author":"Schneeberger","year":"2013","journal-title":"Cell."},{"key":"2023072306244871100_bib39","doi-asserted-by":"publisher","first-page":"5523","DOI":"10.1073\/pnas.1108220109","article-title":"Mitofusin 2 (Mfn2) links mitochondrial and endoplasmic reticulum function with insulin signaling and is essential for normal glucose homeostasis","volume":"109","author":"Sebasti\u00e1n","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072306244871100_bib40","doi-asserted-by":"publisher","first-page":"4512","DOI":"10.1091\/mbc.E04-06-0475","article-title":"The fusome mediates intercellular endoplasmic reticulum connectivity in Drosophila ovarian cysts","volume":"15","author":"Snapp","year":"2004","journal-title":"Mol. Biol. Cell."},{"key":"2023072306244871100_bib41","doi-asserted-by":"crossref","first-page":"226","DOI":"10.2119\/2003-00042.Rodrigues","article-title":"Tauroursodeoxycholic acid prevents amyloid-beta peptide-induced neuronal death via a phosphatidylinositol 3-kinase-dependent signaling pathway","volume":"9","author":"Sol\u00e1","year":"2003","journal-title":"Mol. Med."},{"key":"2023072306244871100_bib42","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1038\/emboj.2009.89","article-title":"SLP-2 is required for stress-induced mitochondrial hyperfusion","volume":"28","author":"Tondera","year":"2009","journal-title":"EMBO J."},{"key":"2023072306244871100_bib43","doi-asserted-by":"publisher","first-page":"5018","DOI":"10.1073\/pnas.0913485107","article-title":"Drosophila parkin requires PINK1 for mitochondrial translocation and ubiquitinates mitofusin","volume":"107","author":"Ziviani","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072306244871100_bib44","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1038\/ng1341","article-title":"Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A","volume":"36","author":"Z\u00fcchner","year":"2004","journal-title":"Nat. Genet."}],"container-title":["Journal of Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jcb\/article-pdf\/204\/3\/303\/1582535\/jcb_201306121.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jcb\/article-pdf\/204\/3\/303\/1582535\/jcb_201306121.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,23]],"date-time":"2023-07-23T06:25:32Z","timestamp":1690093532000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jcb\/article\/204\/3\/303\/37507\/Reduction-of-endoplasmic-reticulum-stress"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1,27]]},"references-count":44,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2014,2,3]]}},"URL":"https:\/\/doi.org\/10.1083\/jcb.201306121","relation":{},"ISSN":["1540-8140","0021-9525"],"issn-type":[{"value":"1540-8140","type":"electronic"},{"value":"0021-9525","type":"print"}],"subject":[],"published":{"date-parts":[[2014,1,27]]}}}