NDLI: Mitochondrial “swirls” induced by oxygen stress and in the Drosophila mutant hyperswirl

Content Provider	PubMed Central
Author	Walker, David W. Benzer, Seymour
Copyright Year	2004
Abstract	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% O2). 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.
Related Links	http://dx.doi.org/10.1073/pnas.0403767101
Ending Page	10295
Page Count	6
Starting Page	10290
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	28
Volume Number	101
Language	English
Publisher	National Academy of Sciences
Publisher Date	2004-07-13
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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