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dc.contributor.authorHaroon, Suraiya
dc.contributor.authorLi, Annie
dc.contributor.authorWeinert, Jaye L.
dc.contributor.authorFritsch, Clark
dc.contributor.authorEricson, Nolan G.
dc.contributor.authorAlexander-Floyd, Jasmine
dc.contributor.authorBraeckman, Bart P.
dc.contributor.authorHaynes, Cole M
dc.contributor.authorBielas, Jason H.
dc.contributor.authorGidalevitz, Tali
dc.contributor.authorVermulst, Marc
dc.date2022-08-11T08:08:22.000
dc.date.accessioned2022-08-23T15:52:58Z
dc.date.available2022-08-23T15:52:58Z
dc.date.issued2018-03-20
dc.date.submitted2018-04-09
dc.identifier.citation<p>Cell Rep. 2018 Mar 20;22(12):3115-3125. doi: 10.1016/j.celrep.2018.02.099. <a href="https://doi.org/10.1016/j.celrep.2018.02.099">Link to article on publisher's site</a></p>
dc.identifier.issn2211-1247 (Electronic)
dc.identifier.doi10.1016/j.celrep.2018.02.099
dc.identifier.pmid29562168
dc.identifier.urihttp://hdl.handle.net/20.500.14038/29259
dc.description.abstractGenetic instability of the mitochondrial genome (mtDNA) plays an important role in human aging and disease. Thus far, it has proven difficult to develop successful treatment strategies for diseases that are caused by mtDNA instability. To address this issue, we developed a model of mtDNA disease in the nematode C. elegans, an animal model that can rapidly be screened for genes and biological pathways that reduce mitochondrial pathology. These worms recapitulate all the major hallmarks of mtDNA disease in humans, including increased mtDNA instability, loss of respiration, reduced neuromuscular function, and a shortened lifespan. We found that these phenotypes could be rescued by intervening in numerous biological pathways, including IGF-1/insulin signaling, mitophagy, and the mitochondrial unfolded protein response, suggesting that it may be possible to ameliorate mtDNA disease through multiple molecular mechanisms.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=29562168&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsThis is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectIGF-1/insulin signaling
dc.subjectRNAi
dc.subjectmitochondrial DNA depletion
dc.subjectmitochondrial disease
dc.subjectmitochondrial genome
dc.subjectmitochondrial unfolded protein response
dc.subjectmitophagy
dc.subjectmutation
dc.subjectneuromuscular dysfunction
dc.subjectpolymerase gamma
dc.subjectCell Biology
dc.subjectCellular and Molecular Physiology
dc.subjectGenetics and Genomics
dc.subjectMolecular Biology
dc.subjectNutritional and Metabolic Diseases
dc.titleMultiple Molecular Mechanisms Rescue mtDNA Disease in C. elegans
dc.typeJournal Article
dc.source.journaltitleCell reports
dc.source.volume22
dc.source.issue12
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2493&amp;context=faculty_pubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/1490
dc.identifier.contextkey11928419
refterms.dateFOA2022-08-23T15:52:59Z
html.description.abstract<p>Genetic instability of the mitochondrial genome (mtDNA) plays an important role in human aging and disease. Thus far, it has proven difficult to develop successful treatment strategies for diseases that are caused by mtDNA instability. To address this issue, we developed a model of mtDNA disease in the nematode C. elegans, an animal model that can rapidly be screened for genes and biological pathways that reduce mitochondrial pathology. These worms recapitulate all the major hallmarks of mtDNA disease in humans, including increased mtDNA instability, loss of respiration, reduced neuromuscular function, and a shortened lifespan. We found that these phenotypes could be rescued by intervening in numerous biological pathways, including IGF-1/insulin signaling, mitophagy, and the mitochondrial unfolded protein response, suggesting that it may be possible to ameliorate mtDNA disease through multiple molecular mechanisms.</p>
dc.identifier.submissionpathfaculty_pubs/1490
dc.contributor.departmentDepartment of Molecular, Cell, and Cancer Biology
dc.contributor.departmentUMass Metabolic Network
dc.source.pages3115-3125


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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Except where otherwise noted, this item's license is described as This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).