{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T09:19:21Z","timestamp":1790155161939,"version":"4.0.1"},"reference-count":94,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,7,23]],"date-time":"2022-07-23T00:00:00Z","timestamp":1658534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Mayo Foundation for Medical Education and Research","award":["DK084567"],"award-info":[{"award-number":["DK084567"]}]},{"name":"Mayo Foundation for Medical Education and Research","award":["GM63904"],"award-info":[{"award-number":["GM63904"]}]},{"name":"Mayo Foundation for Medical Education and Research","award":["HG006431"],"award-info":[{"award-number":["HG006431"]}]},{"name":"Marriott Foundation","award":["DK084567"],"award-info":[{"award-number":["DK084567"]}]},{"name":"Marriott Foundation","award":["GM63904"],"award-info":[{"award-number":["GM63904"]}]},{"name":"Marriott Foundation","award":["HG006431"],"award-info":[{"award-number":["HG006431"]}]},{"name":"NIH","award":["DK084567"],"award-info":[{"award-number":["DK084567"]}]},{"name":"NIH","award":["GM63904"],"award-info":[{"award-number":["GM63904"]}]},{"name":"NIH","award":["HG006431"],"award-info":[{"award-number":["HG006431"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Mitochondria are a dynamic eukaryotic innovation that play diverse roles in biology and disease. The mitochondrial genome is remarkably conserved in all vertebrates, encoding the same 37-gene set and overall genomic structure, ranging from 16,596 base pairs (bp) in the teleost zebrafish (Danio rerio) to 16,569 bp in humans. Mitochondrial disorders are amongst the most prevalent inherited diseases, affecting roughly 1 in every 5000 individuals. Currently, few effective treatments exist for those with mitochondrial ailments, representing a major unmet patient need. Mitochondrial dysfunction is also a common component of a wide variety of other human illnesses, ranging from neurodegenerative disorders such as Huntington\u2019s disease and Parkinson\u2019s disease to autoimmune illnesses such as multiple sclerosis and rheumatoid arthritis. The electron transport chain (ETC) component of mitochondria is critical for mitochondrial biology and defects can lead to many mitochondrial disease symptoms. Here, we present a publicly available collection of genetic mutants created in highly conserved, nuclear-encoded mitochondrial genes in Danio rerio. The zebrafish system represents a potentially powerful new opportunity for the study of mitochondrial biology and disease due to the large number of orthologous genes shared with humans and the many advanced features of this model system, from genetics to imaging. This collection includes 15 mutant lines in 13 different genes created through locus-specific gene editing to induce frameshift or splice acceptor mutations, leading to predicted protein truncation during translation. Additionally, included are 11 lines created by the random insertion of the gene-breaking transposon (GBT) protein trap cassette. All these targeted mutant alleles truncate conserved domains of genes critical to the proper function of the ETC or genes that have been implicated in human mitochondrial disease. This collection is designed to accelerate the use of zebrafish to study many different aspects of mitochondrial function to widen our understanding of their role in biology and human disease.<\/jats:p>","DOI":"10.3390\/genes13081317","type":"journal-article","created":{"date-parts":[[2022,7,24]],"date-time":"2022-07-24T22:49:02Z","timestamp":1658702942000},"page":"1317","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A Primer Genetic Toolkit for Exploring Mitochondrial Biology and Disease Using Zebrafish"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4355-0355","authenticated-orcid":false,"given":"Ankit","family":"Sabharwal","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarryd M.","family":"Campbell","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya L.","family":"Schwab","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"WareJoncas","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark D.","family":"Wishman","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotaka","family":"Ata","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiebin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Division of Cardiovascular Diseases, Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Ichino","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle E.","family":"Hunter","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jake D.","family":"Bergren","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9992-7820","authenticated-orcid":false,"given":"Mark D.","family":"Urban","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhianna M.","family":"Urban","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon R.","family":"Holmberg","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8794-1513","authenticated-orcid":false,"given":"Bibekananda","family":"Kar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Cook","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghe","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Division of Cardiovascular Diseases, Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Division of Cardiovascular Diseases, Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl J.","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0726-4212","authenticated-orcid":false,"given":"Stephen C.","family":"Ekker","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/290457a0","article-title":"Sequence and organization of the human mitochondrial genome","volume":"290","author":"Anderson","year":"1981","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1002\/(SICI)1521-1878(199905)21:5<377::AID-BIES4>3.0.CO;2-W","article-title":"The genome of Rickettsia prowazekii and some thoughts on the origin of mitochondria and hydrogenosomes","volume":"21","author":"Muller","year":"1999","journal-title":"Bioessays"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1126\/science.283.5407.1476","article-title":"Mitochondrial evolution","volume":"283","author":"Gray","year":"1999","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1126\/science.1118884","article-title":"Mutation pressure and the evolution of organelle genomic architecture","volume":"311","author":"Lynch","year":"2006","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0074-7696(08)62223-8","article-title":"Escape and migration of nucleic acids between chloroplasts, mitochondria, and the nucleus","volume":"165","author":"Thorsness","year":"1996","journal-title":"Int. Rev. Cytol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1002\/em.20586","article-title":"Mitochondrial DNA mutations in disease and aging","volume":"51","author":"Wallace","year":"2010","journal-title":"Environ. Mol. Mutagen."},{"key":"ref_7","unstructured":"Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Gripp, K.W., Mirzaa, G.M., and Amemiya, A. (1993). Mitochondrial DNA Deletion Syndromes. GeneReviews((R))."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.mito.2015.08.004","article-title":"The presence of highly disruptive 16S rRNA mutations in clinical samples indicates a wider role for mutations of the mitochondrial ribosome in human disease","volume":"25","author":"Elson","year":"2015","journal-title":"Mitochondrion"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1086\/318801","article-title":"Random intracellular drift explains the clonal expansion of mitochondrial DNA mutations with age","volume":"68","author":"Elson","year":"2001","journal-title":"Am. J. Hum. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1101\/gr.156801","article-title":"The complete sequence of the zebrafish (Danio rerio) mitochondrial genome and evolutionary patterns in vertebrate mitochondrial DNA","volume":"11","author":"Broughton","year":"2001","journal-title":"Genome Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/13779","article-title":"Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA","volume":"23","author":"Andrews","year":"1999","journal-title":"Nat. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S0074-7696(08)62066-5","article-title":"Animal mitochondrial DNA: Structure and evolution","volume":"141","author":"Wolstenholme","year":"1992","journal-title":"Int. Rev. Cytol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1042\/BST0381523","article-title":"Translation termination in human mitochondrial ribosomes","volume":"38","author":"Richter","year":"2010","journal-title":"Biochem. Soc. Trans."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1128\/mr.56.1.229-264.1992","article-title":"Recent evidence for evolution of the genetic code","volume":"56","author":"Osawa","year":"1992","journal-title":"Microbiol. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1093\/hmg\/ddi082","article-title":"Double-strand breaks of mouse muscle mtDNA promote large deletions similar to multiple mtDNA deletions in humans","volume":"14","author":"Srivastava","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.tig.2019.01.001","article-title":"Mechanisms of Mitochondrial DNA Deletion Formation","volume":"35","author":"Nissanka","year":"2019","journal-title":"Trends Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"14392","DOI":"10.1073\/pnas.0502896102","article-title":"Rapid directional shift of mitochondrial DNA heteroplasmy in animal tissues by a mitochondrially targeted restriction endonuclease","volume":"102","author":"Blits","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","first-page":"233","article-title":"Mechanisms of Mitochondrial DNA Repair in Mammals","volume":"83","author":"Zinovkina","year":"2018","journal-title":"Biochemistry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"a012641","DOI":"10.1101\/cshperspect.a012641","article-title":"The maintenance of mitochondrial DNA integrity\u2014Critical analysis and update","volume":"5","author":"Alexeyev","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.cmet.2016.04.004","article-title":"Modifying the Mitochondrial Genome","volume":"23","author":"Patananan","year":"2016","journal-title":"Cell Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.tig.2017.11.001","article-title":"Mitochondrial Genome Engineering: The Revolution May Not Be CRISPR-Ized","volume":"34","author":"Gammage","year":"2018","journal-title":"Trends Genet."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Mok, B.Y., Kotrys, A.V., Raguram, A., Huang, T.P., Mootha, V.K., and Liu, D.R. (2022). CRISPR-free base editors with enhanced activity and expanded targeting scope in mitochondrial and nuclear DNA. Nat. Biotechnol.","DOI":"10.1038\/s41587-022-01256-8"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/s41586-020-2477-4","article-title":"A bacterial cytidine deaminase toxin enables CRISPR-free mitochondrial base editing","volume":"583","author":"Mok","year":"2020","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/s41421-021-00307-9","article-title":"Precision modeling of mitochondrial diseases in zebrafish via DdCBE-mediated mtDNA base editing","volume":"7","author":"Guo","year":"2021","journal-title":"Cell Discov."},{"key":"ref_25","first-page":"799","article-title":"The FusX TALE Base Editor (FusXTBE) for Rapid Mitochondrial DNA Programming of Human Cells In Vitro and Zebrafish Disease Models In Vivo","volume":"4","author":"Sabharwal","year":"2021","journal-title":"CRISPR J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1016\/j.cell.2022.03.039","article-title":"Targeted A-to-G base editing in human mitochondrial DNA with programmable deaminases","volume":"185","author":"Cho","year":"2022","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1038\/s41467-021-21464-1","article-title":"Mitochondrial DNA editing in mice with DddA-TALE fusion deaminases","volume":"12","author":"Lee","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/nature11707","article-title":"Mitochondrial disorders as windows into an ancient organelle","volume":"491","author":"Vafai","year":"2012","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"16080","DOI":"10.1038\/nrdp.2016.80","article-title":"Mitochondrial diseases","volume":"2","author":"Gorman","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"D1541","DOI":"10.1093\/nar\/gkaa1011","article-title":"MitoCarta3.0: An updated mitochondrial proteome now with sub-organelle localization and pathway annotations","volume":"49","author":"Rath","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3427","DOI":"10.1002\/1522-2683(20001001)21:16<3427::AID-ELPS3427>3.0.CO;2-L","article-title":"High-throughput profiling of the mitochondrial proteome using affinity fractionation and automation","volume":"21","author":"Lopez","year":"2000","journal-title":"Electrophoresis"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0076-6879(09)05001-0","article-title":"The mitochondrial proteome database: MitoP2","volume":"457","author":"Elstner","year":"2009","journal-title":"Methods Enzymol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1146\/annurev-genom-091416-035426","article-title":"Recent Advances in Mitochondrial Disease","volume":"18","author":"Craven","year":"2017","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"409","DOI":"10.3233\/JND-150121","article-title":"Adult Onset Leigh Syndrome in the Intensive Care Setting: A Novel Presentation of a C12orf65 Related Mitochondrial Disease","volume":"2","author":"Wesolowska","year":"2015","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1002\/ajmg.a.37138","article-title":"Exome sequencing of patients with histiocytoid cardiomyopathy reveals a de novo NDUFB11 mutation that plays a role in the pathogenesis of histiocytoid cardiomyopathy","volume":"167","author":"Shehata","year":"2015","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Kohda, M., Tokuzawa, Y., Kishita, Y., Nyuzuki, H., Moriyama, Y., Mizuno, Y., Hirata, T., Yatsuka, Y., Yamashita-Sugahara, Y., and Nakachi, Y. (2016). A Comprehensive Genomic Analysis Reveals the Genetic Landscape of Mitochondrial Respiratory Chain Complex Deficiencies. PLoS Genet., 12.","DOI":"10.1371\/journal.pgen.1005679"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.ajhg.2008.08.009","article-title":"FASTKD2 nonsense mutation in an infantile mitochondrial encephalomyopathy associated with cytochrome c oxidase deficiency","volume":"83","author":"Ghezzi","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.molcel.2016.06.033","article-title":"Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function","volume":"63","author":"Floyd","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/978-1-59745-365-3_6","article-title":"Saccharomyces cerevisiae as a model organism to study mitochondrial biology: General considerations and basic procedures","volume":"372","author":"Altmann","year":"2007","journal-title":"Methods Mol. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1111\/1574-6976.12060","article-title":"Budding yeast as a model organism to study the effects of age","volume":"38","author":"Julou","year":"2014","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1002\/biot.200500053","article-title":"Yeast models of human mitochondrial diseases: From molecular mechanisms to drug screening","volume":"1","author":"Schwimmer","year":"2006","journal-title":"Biotechnol. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/j.bbadis.2010.05.007","article-title":"Caenorhabditis elegans, a pluricellular model organism to screen new genes involved in mitochondrial genome maintenance","volume":"1802","author":"Addo","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_43","first-page":"705253","article-title":"Caenorhabditis elegans: A useful model for studying metabolic disorders in which oxidative stress is a contributing factor","volume":"2014","year":"2014","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1080\/07924259.2014.940470","article-title":"Using C. elegans for aging research","volume":"59","author":"Tissenbaum","year":"2015","journal-title":"Invertebr. Reprod. Dev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/978-1-59745-365-3_3","article-title":"Drosophila melanogaster as a model system to study mitochondrial biology","volume":"372","author":"Farr","year":"2007","journal-title":"Methods Mol. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"a009944","DOI":"10.1101\/cshperspect.a009944","article-title":"Drosophila as a model to study mitochondrial dysfunction in Parkinson\u2019s disease","volume":"2","author":"Guo","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1016\/j.bbabio.2006.05.008","article-title":"Modeling human mitochondrial diseases in flies","volume":"1757","author":"Luo","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.ctdb.2016.07.001","article-title":"Fly Models of Human Diseases: Drosophila as a Model for Understanding Human Mitochondrial Mutations and Disease","volume":"121","author":"Sen","year":"2017","journal-title":"Curr. Top. Dev. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4872","DOI":"10.1074\/jbc.273.9.4872","article-title":"The respiratory chain in yeast behaves as a single functional unit","volume":"273","author":"Boumans","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1073\/pnas.76.4.1967","article-title":"Rapid evolution of animal mitochondrial DNA","volume":"76","author":"Brown","year":"1979","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.jmb.2010.09.029","article-title":"Coevolution predicts direct interactions between mtDNA-encoded and nDNA-encoded subunits of oxidative phosphorylation complex i","volume":"404","author":"Gershoni","year":"2010","journal-title":"J. Mol. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.tig.2004.09.002","article-title":"Accelerated evolution of the electron transport chain in anthropoid primates","volume":"20","author":"Grossman","year":"2004","journal-title":"Trends Genet."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2216","DOI":"10.1093\/molbev\/msq112","article-title":"Parallel loss of nuclear-encoded mitochondrial aminoacyl-tRNA synthetases and mtDNA-encoded tRNAs in Cnidaria","volume":"27","author":"Haen","year":"2010","journal-title":"Mol. Biol. Evol."},{"key":"ref_54","first-page":"855","article-title":"Protein biosynthesis in mitochondria","volume":"78","author":"Kuzmenko","year":"2013","journal-title":"Biochemistry"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2896","DOI":"10.1093\/gbe\/evw195","article-title":"Animal Mitochondrial DNA as We Do Not Know It: Mt-Genome Organization and Evolution in Nonbilaterian Lineages","volume":"8","author":"Lavrov","year":"2016","journal-title":"Genome Biol. Evol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2496","DOI":"10.1016\/j.febslet.2014.05.054","article-title":"Mitochondrial protein synthesis: Figuring the fundamentals, complexities and complications, of mammalian mitochondrial translation","volume":"588","author":"Lightowlers","year":"2014","journal-title":"FEBS Lett."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1093\/gbe\/evv124","article-title":"Cytonuclear Interactions in the Evolution of Animal Mitochondrial tRNA Metabolism","volume":"7","author":"Pett","year":"2015","journal-title":"Genome Biol. Evol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1002\/ddrr.114","article-title":"Bacteria, yeast, worms, and flies: Exploiting simple model organisms to investigate human mitochondrial diseases","volume":"16","author":"Rea","year":"2010","journal-title":"Dev. Disabil. Res. Rev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1007\/s00018-012-1066-6","article-title":"Regulation of mitochondrial dynamics: Convergences and divergences between yeast and vertebrates","volume":"70","author":"Zhao","year":"2013","journal-title":"Cell Mol. Life Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/bs.mcb.2016.10.006","article-title":"Zebrafish models of human eye and inner ear diseases","volume":"138","author":"Clement","year":"2017","journal-title":"Methods Cell Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s12929-016-0236-5","article-title":"Zebrafish and Medaka: New model organisms for modern biomedical research","volume":"23","author":"Lin","year":"2016","journal-title":"J. Biomed. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/nrg2091","article-title":"Animal models of human disease: Zebrafish swim into view","volume":"8","author":"Lieschke","year":"2007","journal-title":"Nat. Rev. Genet."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Fichi, G., Naef, V., Barca, A., Longo, G., Fronte, B., Verri, T., Santorelli, F.M., Marchese, M., and Petruzzella, V. (2019). Fishing in the Cell Powerhouse: Zebrafish as A Tool for Exploration of Mitochondrial Defects Affecting the Nervous System. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20102409"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.trsl.2013.08.008","article-title":"Zebrafish as a model system for mitochondrial biology and diseases","volume":"163","author":"Steele","year":"2014","journal-title":"Transl. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"331","DOI":"10.2144\/000112909","article-title":"Real-time imaging of mitochondria in transgenic zebrafish expressing mitochondrially targeted GFP","volume":"45","author":"Kim","year":"2008","journal-title":"Biotechniques"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1111\/bph.12186","article-title":"How mitochondrial dysfunction affects zebrafish development and cardiovascular function: An in vivo model for testing mitochondria-targeted drugs","volume":"169","author":"Pinho","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.ymgme.2018.02.013","article-title":"N-acetylcysteine and vitamin E rescue animal longevity and cellular oxidative stress in pre-clinical models of mitochondrial complex I disease","volume":"123","author":"Polyak","year":"2018","journal-title":"Mol. Genet. Metab."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1126\/science.aad9642","article-title":"Hypoxia as a therapy for mitochondrial disease","volume":"352","author":"Jain","year":"2016","journal-title":"Science"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.neuint.2017.07.008","article-title":"Pharmacologic modeling of primary mitochondrial respiratory chain dysfunction in zebrafish","volume":"117","author":"Byrnes","year":"2018","journal-title":"Neurochem. Int."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3389\/fncel.2017.00004","article-title":"In vivo Imaging of Mitochondrial Transport in Single-Axon Regeneration of Zebrafish Mauthner Cells","volume":"11","author":"Xu","year":"2017","journal-title":"Front. Cell. Neurosci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1093\/brain\/aws036","article-title":"Oxidative stress and successful antioxidant treatment in models of RYR1-related myopathy","volume":"135","author":"Dowling","year":"2012","journal-title":"Brain"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Song, Y., Selak, M.A., Watson, C.T., Coutts, C., Scherer, P.C., Panzer, J.A., Gibbs, S., Scott, M.O., Willer, G., and Gregg, R.G. (2009). Mechanisms underlying metabolic and neural defects in zebrafish and human multiple acyl-CoA dehydrogenase deficiency (MADD). PLoS One, 4.","DOI":"10.1371\/journal.pone.0008329"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e38062","DOI":"10.7554\/eLife.38062","article-title":"Cumulative mitochondrial activity correlates with ototoxin susceptibility in zebrafish mechanosensory hair cells","volume":"7","author":"Pickett","year":"2018","journal-title":"Elife"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"144","DOI":"10.3389\/fcell.2018.00144","article-title":"Analyzing Neuronal Mitochondria in vivo Using Fluorescent Reporters in Zebrafish","volume":"6","author":"Mandal","year":"2018","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"16203","DOI":"10.1523\/JNEUROSCI.1327-12.2012","article-title":"In vivo imaging of disease-related mitochondrial dynamics in a vertebrate model system","volume":"32","author":"Plucinska","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Liu, T.L., Upadhyayula, S., Milkie, D.E., Singh, V., Wang, K., Swinburne, I.A., Mosaliganti, K.R., Collins, Z.M., Hiscock, T.W., and Shea, J. (2018). Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms. Science, 360.","DOI":"10.1126\/science.aaq1392"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1089\/hum.2015.172","article-title":"FusX: A Rapid One-Step Transcription Activator-Like Effector Assembly System for Genome Science","volume":"27","author":"Ma","year":"2016","journal-title":"Hum. Gene Ther."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/nmeth.1606","article-title":"In vivo protein trapping produces a functional expression codex of the vertebrate proteome","volume":"8","author":"Clark","year":"2011","journal-title":"Nat. Methods"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e54572","DOI":"10.7554\/eLife.54572","article-title":"Building the vertebrate codex using the gene breaking protein trap library","volume":"9","author":"Ichino","year":"2020","journal-title":"Elife"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Neff, K.L., Argue, D.P., Ma, A.C., Lee, H.B., Clark, K.J., and Ekker, S.C. (2013). Mojo Hand, a TALEN design tool for genome editing applications. BMC Bioinform., 14.","DOI":"10.1186\/1471-2105-14-1"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"4252","DOI":"10.1073\/pnas.0500607102","article-title":"On the utility of pooling biological samples in microarray experiments","volume":"102","author":"Kendziorski","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nbt.3519","article-title":"Near-optimal probabilistic RNA-seq quantification","volume":"34","author":"Bray","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.12688\/f1000research.7563.1","article-title":"Differential analyses for RNA-seq: Transcript-level estimates improve gene-level inferences","volume":"4","author":"Soneson","year":"2015","journal-title":"F1000Research"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"W515","DOI":"10.1093\/nar\/gkaa306","article-title":"GeneTrail 3: Advanced high-throughput enrichment analysis","volume":"48","author":"Gerstner","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/s41596-019-0128-8","article-title":"Protocol Update for large-scale genome and gene function analysis with the PANTHER classification system (v.14.0)","volume":"14","author":"Mi","year":"2019","journal-title":"Nat. Protoc."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"D907","DOI":"10.1093\/nar\/gkr957","article-title":"zfishbook: Connecting you to a world of zebrafish revertible mutants","volume":"40","author":"Clark","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.2174\/092986709787846578","article-title":"Mitochondrial respiratory complex I: Structure, function and implication in human diseases","volume":"16","author":"Sharma","year":"2009","journal-title":"Curr. Med. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1126\/science.2814477","article-title":"Human cells lacking mtDNA: Repopulation with exogenous mitochondria by complementation","volume":"246","author":"King","year":"1989","journal-title":"Science"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"S119","DOI":"10.1002\/mus.880181424","article-title":"Analysis of cybrids harboring MELAS mutations in the mitochondrial tRNA(Leu(UUR)) gene","volume":"3","author":"Koga","year":"1995","journal-title":"Muscle Nerve Suppl."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.redox.2014.03.006","article-title":"Cytoplasmic hybrid (cybrid) cell lines as a practical model for mitochondriopathies","volume":"2","author":"Wilkins","year":"2014","journal-title":"Redox Biol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nbt.2501","article-title":"Efficient genome editing in zebrafish using a CRISPR-Cas system","volume":"31","author":"Hwang","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/nature11537","article-title":"In vivo genome editing using a high-efficiency TALEN system","volume":"491","author":"Bedell","year":"2012","journal-title":"Nature"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Sabharwal, A., Wishman, M.D., Cervera, R.L., Serres, M.R., Anderson, J.L., Treichel, A.J., Ichino, N., Liu, W., Yang, J., and Ding, Y. (2000). A Genetic Model Therapy Proposes a Critical Role for Liver Dysfunction in Mitochondrial Biology and Disease. bioRxiv, 2020.2005.2008.084681.","DOI":"10.1101\/2020.05.08.084681"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/8\/1317\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:55:35Z","timestamp":1760140535000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/8\/1317"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,23]]},"references-count":94,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["genes13081317"],"URL":"https:\/\/doi.org\/10.3390\/genes13081317","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/542084","asserted-by":"object"}]},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,23]]}}}