RRC ID 45972
Author Ghose P, Park EC, Tabakin A, Salazar-Vasquez N, Rongo C.
Title Anoxia-reoxygenation regulates mitochondrial dynamics through the hypoxia response pathway, SKN-1/Nrf, and stomatin-like protein STL-1/SLP-2.
Journal PLoS Genet
Abstract Many aerobic organisms encounter oxygen-deprived environments and thus must have adaptive mechanisms to survive such stress. It is important to understand how mitochondria respond to oxygen deprivation given the critical role they play in using oxygen to generate cellular energy. Here we examine mitochondrial stress response in C. elegans, which adapt to extreme oxygen deprivation (anoxia, less than 0.1% oxygen) by entering into a reversible suspended animation state of locomotory arrest. We show that neuronal mitochondria undergo DRP-1-dependent fission in response to anoxia and undergo refusion upon reoxygenation. The hypoxia response pathway, including EGL-9 and HIF-1, is not required for anoxia-induced fission, but does regulate mitochondrial reconstitution during reoxygenation. 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. Mitochondria are significantly larger in egl-9 mutants after reoxygenation, a phenotype similar to stress-induced mitochondria hyperfusion (SIMH). 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. 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. Our results suggest the existence of a conserved anoxic stress response involving changes in mitochondrial fission and fusion.
Volume 9(12)
Pages e1004063
Published 2013-1-1
DOI 10.1371/journal.pgen.1004063
PMID 24385935
PMC PMC3873275
MeSH Aerobiosis / genetics* Aerobiosis / physiology Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Cell Hypoxia / genetics Cell Hypoxia / physiology Dynamins / metabolism Hypoxia / genetics Mitochondria / genetics Mitochondria / metabolism Mitochondria / physiology* Mitochondrial Dynamics / genetics Mitochondrial Proteins / genetics* NF-E2-Related Factor 1 / genetics* NF-E2-Related Factor 1 / metabolism Neurons / cytology Neurons / metabolism Neurons / physiology* Oxidation-Reduction Oxidative Stress / genetics Transcription Factors / metabolism
IF 5.175
Times Cited 23
C.elegans tm1544 tm3411