title: The epsilon-subunit of mitochondrial ATP synthase is required for normal spindle orientation during the Drosophila embryonic divisions.
abstract: We describe the maternal-effect and zygotic phenotypes of null mutations in the Drosophila gene for the epsilon-subunit of mitochondrial ATP synthase, stunted (sun). Loss of zygotic sun expression leads to a dramatic delay in the growth rate of first instar larvae and ultimately death. Embryos lacking maternally supplied sun (sun embryos) have a sixfold reduction in ATP synthase activity. Cellular analysis of sun embryos shows defects only after the nuclei have migrated to the cortex. During the cortical divisions the actin-based metaphase and cellularization furrows do not form properly, and the nuclei show abnormal spacing and division failures. The most striking abnormality is that nuclei and spindles form lines and clusters, instead of adopting a regular spacing. This is reflected in a failure to properly position neighboring nonsister centrosomes during the telophase-to-interphase transition of the cortical divisions. Our study is consistent with a role for Sun in mitochondrial ATP synthesis and suggests that reduced ATP levels selectively affect molecular motors. As Sun has been identified as the ligand for the Methuselah receptor that regulates aging, Sun may function both within and outside mitochondria.
authors.affiliation: Developmental Genetics Laboratory, Cancer Research UK, London, England. tkidd@unr.edu
authors.forename: Thomas
authors.initials: T
authors.lastname: Kidd
authors.forename: Robin
authors.initials: R
authors.lastname: Abu-Shumays
authors.forename: Alisa
authors.initials: A
authors.lastname: Katzen
authors.forename: John C
authors.initials: JC
authors.lastname: Sisson
authors.forename: Gerardo
authors.initials: G
authors.lastname: Jiménez
authors.forename: Sheena
authors.initials: S
authors.lastname: Pinchin
authors.forename: William
authors.initials: W
authors.lastname: Sullivan
authors.forename: David
authors.initials: D
authors.lastname: Ish-Horowicz
mesh_terms: D000199:Actins / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D018385:Centrosome / Q000648:ultrastructure; D003599:Cytoskeleton / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004330:Drosophila / Q000196:embryology* / Q000502:physiology; D005260:Female; D007399:Interphase; D008024:Ligands; D008297:Male; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D025261:Mitochondrial Proton-Translocating ATPases / Q000737:chemistry* / Q000502:physiology; D008957:Models, Genetic; D008958:Models, Molecular; D020409:Molecular Motor Proteins; D008969:Molecular Sequence Data; D010641:Phenotype; D017386:Sequence Homology, Amino Acid; D008941:Spindle Apparatus; D013692:Telophase
chemical_list: D000199:Actins; D008024:Ligands; D020409:Molecular Motor Proteins; D000255:Adenosine Triphosphate; D004247:DNA; D000251:Adenosine Triphosphatases; D025261:Mitochondrial Proton-Translocating ATPases