Originally published as Genetics Published Articles Ahead of Print on April 16, 2005.

Genetics, Vol. 170, 697-708, June 2005, Copyright © 2005
doi:10.1534/genetics.104.037648

The -Subunit of Mitochondrial ATP Synthase Is Required for Normal Spindle Orientation During the Drosophila Embryonic Divisions

Thomas Kidd^*,,1,2, Robin Abu-Shumays^,1,3, Alisa Katzen, John C. Sisson^,4, Gerardo Jiménez^*,5, Sheena Pinchin^*, William Sullivan and David Ish-Horowicz^*

^* Developmental Genetics Laboratory, Cancer Research UK, London WC2A 3PX, England
Department of Biology, Sinsheimer Laboratories, University of California, Santa Cruz, California 95064
Department of Biochemistry and Molecular Genetics, University of Illinois College of Medicine, Chicago, Illinois 60607-7170
Department of Biology, University of Nevada, Reno, Nevada 89557

² Corresponding author: Biology/ms 314, 1664 N. Virginia St., University of Nevada, Reno, NV 89557.
E-mail: tkidd{at}unr.edu

We describe the maternal-effect and zygotic phenotypes of null mutations in the Drosophila gene for the -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.

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