Hypoxia-adaptation involves mitochondrial metabolic depression and decreased ROS leakage

Through long-term laboratory selection, we have generated a Drosophila melanogaster population that tolerates severe, normally lethal, level of hypoxia. This strain lives perpetually under severe hypoxic conditions (4% O(2)). In order to shed light on the mechanisms involved in this adaptation, we s...

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Published in:	PloS one 2012-05, Vol.7 (5), p.e36801
Main Authors:	Ali, Sameh S, Hsiao, Mary, Zhao, Huiwen W, Dugan, Laura L, Haddad, Gabriel G, Zhou, Dan
Format:	Article
Language:	eng
Subjects:	Adaptation Adaptation, Physiological Aging Animals Apoptosis Basal Metabolism Biology Cancer Cell Respiration Cytochrome Drosophila melanogaster Drosophila melanogaster - cytology Drosophila melanogaster - metabolism Drosophila melanogaster - physiology Electron paramagnetic resonance Electron transport Electron Transport Chain Complex Proteins - metabolism Flies Gene expression Hypoxia Insects Leakage Male Metabolic depression Metabolism Mitochondria Mitochondria - metabolism Neurosciences Oxidation-Reduction Oxidative stress Oxygen Oxygen - metabolism Oxygen consumption Paramagnetic resonance Pediatrics Phosphorylation Principal components analysis Pulmonary arteries Reactive Oxygen Species - metabolism Respiration Respiratory function Respiratory rate Succinate dehydrogenase Superoxide Superoxides Superoxides - metabolism Thorax Tumorigenesis
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Summary:	Through long-term laboratory selection, we have generated a Drosophila melanogaster population that tolerates severe, normally lethal, level of hypoxia. This strain lives perpetually under severe hypoxic conditions (4% O(2)). In order to shed light on the mechanisms involved in this adaptation, we studied the respiratory function of isolated mitochondria from the thorax of hypoxia-adapted flies (AF) using polarographic oxygen consumption while monitoring superoxide generation by electron paramagnetic resonance (EPR) techniques. AF mitochondria exhibited a significant 30% decrease in respiratory rate during state 3, while enhancing the resting respiratory rate during State 4-oligo by 220%. The activity of individual electron transport complexes I, II and III were 107%, 65%, and 120% in AF mitochondria as compared to those isolated from control flies. The sharp decrease in complex II activity and modest increase in complexes I and III resulted in >60% reduction in superoxide leakage from AF mitochondria during both NAD(+)-linked state 3 and State 4-oligo respirations. These results provide evidence that flies with mitochondria exhibiting decreased succinate dehydrogenase activity and reduced superoxide leakage give flies an advantage for survival in long-term hypoxia.
ISSN:	1932-6203 1932-6203