Zivkovic G, Buck LT (2010) Regulation of AMPA receptor currents by mitochondrial ATP-sensitive K+ channels in anoxic turtle neurons. N = 15–35 animals per condition and/or genotype. ANOVA followed by Dunnett's multiple comparison to wild type, normoxia (#p<0.001, **p<0.01, *p<0.05). Red bars indicate normoxia, blue bars indicate anoxia, and purple stippled bars indicate reoxygenation. (R) Quantification of behavioral recovery (number of animals moving after 10 minutes of reoxygenation) of animals following 24 hours anoxia. (P,Q) Quantification of the mean (P) length and (Q) number of mitochondria along the ventral cord for the indicated genotypes and conditions. Conditions included (A,D,G,J,M) normoxia, (B,E,H,K,N) following 24 hours of anoxia, or (C,F,I,L,O) following 3 hours of reoxygenation post-anoxia. The fluorescence of MitoGFP was observed along ventral cord neurites of (A,B,C) wild-type animals, (D,E,F) egl-9(sa307) mutants, (G,H,I) hif-1(ia4) mutants, (J,K,L) egl-9(sa307) hif-1(ia4) double mutants, and (M,N,O) egl-9 mutants with a transgene expressing the wild-type EGL-9A cDNA from the glr-1 promoter. Our results suggest the existence of a conserved anoxic stress response involving changes in mitochondrial fission and fusion. In response to anoxia, SKN-1 promotes the expression of the mitochondrial resident protein Stomatin-like 1 (STL-1), which helps facilitate mitochondrial dynamics following anoxia. Anoxia results in mitochondrial oxidative stress, and the oxidative response factor SKN-1/Nrf is required for both rapid mitochondrial refusion and rapid behavioral recovery during reoxygenation. Mitochondria are significantly larger in egl-9 mutants after reoxygenation, a phenotype similar to stress-induced mitochondria hyperfusion (SIMH). Mutants for egl-9 exhibit a rapid refusion of mitochondria and a rapid behavioral recovery from suspended animation during reoxygenation both phenotypes require HIF-1. The hypoxia response pathway, including EGL-9 and HIF-1, is not required for anoxia-induced fission, but does regulate mitochondrial reconstitution during reoxygenation. We show that neuronal mitochondria undergo DRP-1-dependent fission in response to anoxia and undergo refusion upon reoxygenation.
elegans, which adapt to extreme oxygen deprivation (anoxia, less than 0.1% oxygen) by entering into a reversible suspended animation state of locomotory arrest. Here we examine mitochondrial stress response in C. It is important to understand how mitochondria respond to oxygen deprivation given the critical role they play in using oxygen to generate cellular energy. Many aerobic organisms encounter oxygen-deprived environments and thus must have adaptive mechanisms to survive such stress.
0 kommentar(er)
