RRC ID 65246
Author Machiela E, Liontis T, Dues DJ, Rudich PD, Traa A, Wyman L, Kaufman C, Cooper JF, Lew L, Nadarajan S, Senchuk MM, Van Raamsdonk JM.
Title Disruption of mitochondrial dynamics increases stress resistance through activation of multiple stress response pathways.
Journal FASEB J
Abstract Mitochondria are dynamic organelles that can change shape and size depending on the needs of the cell through the processes of mitochondrial fission and fusion. In this work, we investigated the role of mitochondrial dynamics in organismal stress response. By using C. elegans as a genetic model, we could visualize mitochondrial morphology in a live organism with well-established stress assays and well-characterized stress response pathways. We found that disrupting mitochondrial fission (DRP1/drp-1) or fusion (OPA1/eat-3, MFN/fzo-1) genes caused alterations in mitochondrial morphology that impacted both mitochondrial function and physiologic rates. While both mitochondrial fission and mitochondrial fusion mutants showed increased sensitivity to osmotic stress and anoxia, surprisingly we found that the mitochondrial fusion mutants eat-3 and fzo-1 are more resistant to both heat stress and oxidative stress. In exploring the mechanism of increased stress resistance, we found that disruption of mitochondrial fusion genes resulted in the upregulation of multiple stress response pathways. Overall, this work demonstrates that disrupting mitochondrial dynamics can have opposite effects on resistance to different types of stress. Our results suggest that disruption of mitochondrial fusion activates multiple stress response pathways that enhance resistance to specific stresses.
Volume 34(6)
Pages 8475-8492
Published 2020-6-1
DOI 10.1096/fj.201903235R
PMID 32385951
PMC PMC7313680
MeSH Animals Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / metabolism Dynamins / metabolism GTP Phosphohydrolases / metabolism Mitochondria / metabolism* Mitochondrial Dynamics / physiology* Mitochondrial Proteins / metabolism Organelles / metabolism Oxidative Stress / physiology* Stress, Physiological / physiology*
Resource
C.elegans tm1107 tm1108 tm1133 tm1867 tm2955 tm3041