Tolerance to low O2: lessons from invertebrate genetic models
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Published on: July 20, 2012
1Department of Pediatrics, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0735, USA. ghaddad@ucsd.edu
Abstract:
There have been extensive studies and experiments on cells, tissues and animals that are susceptible to low O2, and many pathways have been discovered that can lead to injury in mammalian tissues. But other pathways that can help in the survival of low O2 have also been discovered in these same tissues. It should be noted, however, that the mechanisms that can lead to better survival in susceptible mammalian tissues have quantitatively a 'narrow range' for recovery, since these tissues are inherently at risk. Another strategy for understanding the susceptibility of organisms is to learn about pathways used by anoxia-resistant animals. Approximately a decade ago, I and my co-workers discovered that one such animal, Drosophila melanogaster, is very tolerant of low O2. Here, I detail some of the studies that we performed and the strategies that we developed to understand the mechanisms that underlie the fascinating resistance of Drosophila to measured partial pressure of O2 of zero. We employed three ideas to try to address our questions: (1) mutagenesis screens to identify loss-of-function mutants; (2) microarrays on adapted versus naïve flies; and (3) studying cell biology and physiology of genes that seem important in flies and mammals. The hope is to learn from these studies about the fundamental basis of tolerance to the lack of O2, and with this knowledge be able to develop better therapies for the future.
Insights
Fruit flies, Drosophila melanogaster, exhibit remarkable tolerance to zero oxygen levels. Studying their survival mechanisms offers insights into fundamental oxygen deprivation tolerance and potential therapies.
Area of Science:
- Molecular Biology
- Genetics
- Physiology
Background:
- Mammalian tissues exhibit susceptibility to low oxygen (hypoxia), with identified pathways for both injury and survival, though recovery ranges are narrow.
- Anoxia-resistant animals offer alternative strategies for understanding oxygen deprivation tolerance.
- Drosophila melanogaster (fruit fly) has been identified as highly tolerant to near-zero oxygen levels.
Discussion:
- Investigated mechanisms of Drosophila's resistance to extreme hypoxia using mutagenesis screens for loss-of-function mutants.
- Employed microarrays to compare gene expression in adapted versus naive flies under low oxygen conditions.
- Examined the cell biology and physiology of genes crucial for oxygen tolerance in both flies and mammals.
Key Insights:
- Drosophila melanogaster demonstrates significant tolerance to anoxia, providing a model for studying oxygen deprivation survival.
- Comparative studies between Drosophila and mammals highlight conserved and unique pathways involved in oxygen tolerance.
- Genetic and physiological approaches reveal key molecular players underlying resistance to low oxygen.
Outlook:
- Understanding the fundamental basis of oxygen deprivation tolerance in Drosophila can inform the development of novel therapeutic strategies for hypoxia-related conditions in humans.
- Further research on conserved genes and pathways may lead to interventions for improving tissue survival during oxygen scarcity.
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