title: Hypoxia-adaptation involves mitochondrial metabolic depression and decreased ROS leakage.
abstract: 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.
authors.affiliation: Department of Medicine, University of California San Diego, San Diego, California, United States of America. ssali@ucsd.edu
authors.forename: Sameh S
authors.initials: SS
authors.lastname: Ali
authors.forename: Mary
authors.initials: M
authors.lastname: Hsiao
authors.forename: Huiwen W
authors.initials: HW
authors.lastname: Zhao
authors.forename: Laura L
authors.initials: LL
authors.lastname: Dugan
authors.forename: Gabriel G
authors.initials: GG
authors.lastname: Haddad
authors.forename: Dan
authors.initials: D
authors.lastname: Zhou
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001481:Basal Metabolism; D019069:Cell Respiration; D004331:Drosophila melanogaster / Q000166:cytology* / Q000378:metabolism* / Q000502:physiology; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
chemical_list: D045222:Electron Transport Chain Complex Proteins; D017382:Reactive Oxygen Species; D013481:Superoxides; D010100:Oxygen