title: Opa1 is required for proper mitochondrial metabolism in early development.
abstract: Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae. OPA1 mutations in humans lead to autosomal dominant optic atrophy. OPA1 knockout mice lose viability around embryonic day 9 from unknown reasons, indicating that OPA1 is essential for embryonic development. Zebrafish are an attractive model for studying vertebrate development and have been used for many years to describe developmental events that are difficult or impractical to view in mammalian models. In this study, Opa1 was successfully depleted in zebrafish embryos using antisense morpholinos, which resulted in disrupted mitochondrial morphology. Phenotypically, these embryos exhibited abnormal blood circulation and heart defects, as well as small eyes and small pectoral fin buds. Additionally, startle response was reduced and locomotor activity was impaired. Furthermore, Opa1 depletion caused bioenergetic defects, without impairing mitochondrial efficiency. In response to mitochondrial dysfunction, a transient upregulation of the master regulator of mitochondrial biogenesis, pgc1a, was observed. These results not only reveal a new Opa1-associated phenotype in a vertebrate model system, but also further elucidates the absolute requirement of Opa1 for successful vertebrate development.
authors.affiliation: Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina, United States of America.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Rahn
authors.forename: Krista D
authors.initials: KD
authors.lastname: Stackley
authors.forename: Sherine S L
authors.initials: SS
authors.lastname: Chan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D060172:Morpholinos / Q000494:pharmacology; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D060172:Morpholinos; D029961:Zebrafish Proteins