Walker, David W. and Benzer, Seymour (2004) Mitochondrial "swirls" induced by oxygen stress and in the Drosophila mutant hyperswirl. Proceedings of the National Academy of Sciences of the United States of America, 101 (28). pp. 10290-10295. ISSN 0027-8424 http://resolver.caltech.edu/CaltechAUTHORS:WALpnas04
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Mitochondrial dysfunction and reactive oxygen species have been implicated in the aging process as well as a wide range of hereditary and age-related diseases. Identifying primary events that result from acute oxidative stress may provide targets for therapeutic interventions that preclude aging. By using electron microscopy, we have discovered a striking initial pattern of degeneration of the mitochondria in Drosophila flight muscle under hyperoxia (100% O-2). Within individual mitochondria, the cristae become locally rearranged in a pattern that we have termed a "swirl." Serial sections through individual mitochondria reveal the reorganization of the cristae in three dimensions. The cristae involved in a swirl are deficient in respiratory enzyme cytochrome c oxidase activity, within an otherwise cytochrome c oxidase-positive mitochondrion. In addition, under hyperoxia cytochrome c undergoes a conformational change, manifested by display of an otherwise hidden epitope. The conformational change is correlated with widespread apoptotic cell death in the flight muscle, as revealed by in situ terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling. In normal flies, mitochondrial swirls accumulate slowly with age. To investigate the molecular mechanisms involved in oxygen toxicity, we conducted a genetic screen for mutants that display altered survival under hyperoxia, and we identified both sensitive and resistant mutants. We describe a mutant, hyperswirl, which displays an overabundance of swirls with associated respiratory and flight defects and a greatly reduced lifespan. Such mutants can identify genes that are needed to maintain mitochondrial homeostasis throughout the lifespan.
|Additional Information:||Copyright © 2004 by the National Academy of Sciences. Contributed by Seymour Benzer, May 28, 2004. Published online before print June 30, 2004, 10.1073/pnas.0403767101 From the cover. We thank Rosalind Young and Stephanie Cornelison for expert technical assistance; R. Jemmerson for kindly providing mAb 2G8; Anne Simon for help with the flight assay; Laurent Seroude for sharing the electron micrographs of old flies; and Petr Hajek, Giuseppe Attardi, and members of the Benzer lab for helpful discussions. D.W.W. was supported by a Wellcome Trust Prize Traveling Research Fellowship. This work was funded by grants from the Ellison Medical Foundation, the National Science Foundation, and the National Institute on Aging (to S.B.).|
|Subject Keywords:||hyperoxia, aging, cytochrome C, apoptosis, muscle, life-span, oxidative stress, superoxide-dismutase, flight muscle, cell-death, melanogaster, overexpression, damage, extension|
|Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Tony Diaz|
|Deposited On:||13 Dec 2005|
|Last Modified:||26 Dec 2012 08:42|
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