title: Ultrastructural modifications in the mitochondria of hypoxia-adapted Drosophila melanogaster.
abstract: Chronic hypoxia (CH) occurs under certain physiological or pathological conditions, including in people who reside at high altitude or suffer chronic cardiovascular or pulmonary diseases. As mitochondria are the predominant oxygen-consuming organelles to generate ATP through oxidative phosphorylation in cells, their responses, through structural or molecular modifications, to limited oxygen supply play an important role in the overall functional adaptation to hypoxia. Here, we report the adaptive mitochondrial ultrastructural modifications and the functional impacts in a recently generated hypoxia-adapted Drosophila melanogaster strain that survives severe, otherwise lethal, hypoxic conditions. Using electron tomography, we discovered increased mitochondrial volume density and cristae abundance, yet also cristae fragmentation and a unique honeycomb-like structure in the mitochondria of hypoxia-adapted flies. The homeostatic levels of adenylate and energy charge were similar between hypoxia-adapted and naïve control flies and the hypoxia-adapted flies remained active under severe hypoxia as quantified by negative geotaxis behavior. The equilibrium ATP level was lower in hypoxia-adapted flies than those of the naïve controls tested under severe hypoxia that inhibited the motion of control flies. Our results suggest that the structural rearrangement in the mitochondria of hypoxia-adapted flies may be an important adaptive mechanism that plays a critical role in preserving adenylate homeostasis and metabolism as well as muscle function under chronic hypoxic conditions.
authors.affiliation: National Center for Microscopy and Imaging Research, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Guy
authors.initials: G
authors.lastname: Perkins
authors.forename: Yu-hsin
authors.initials: YH
authors.lastname: Hsiao
authors.forename: Songyue
authors.initials: S
authors.lastname: Yin
authors.forename: Jonathan
authors.initials: J
authors.lastname: Tjong
authors.forename: My T
authors.initials: MT
authors.lastname: Tran
authors.forename: Jenna
authors.initials: J
authors.lastname: Lau
authors.forename: Jin
authors.initials: J
authors.lastname: Xue
authors.forename: Siqi
authors.initials: S
authors.lastname: Liu
authors.forename: Mark H
authors.initials: MH
authors.lastname: Ellisman
authors.forename: Dan
authors.initials: D
authors.lastname: Zhou
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004331:Drosophila melanogaster / Q000502:physiology* / Q000648:ultrastructure*; D000860:Hypoxia / Q000503:physiopathology*; D008928:Mitochondria / Q000502:physiology* / Q000648:ultrastructure*; D018384:Oxidative Stress / Q000502:physiology
chemical_list: D000255:Adenosine Triphosphate