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 |