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Disruption of mitochondrial dynamics increases stress resistance through activation of multiple stress response pathways
Author(s) -
Machiela Emily,
Liontis Thomas,
Dues Dylan J.,
Rudich Paige D.,
Traa Annika,
Wyman Leslie,
Kaufman Corah,
Cooper Jason F.,
Lew Leira,
Nadarajan Saravanapriah,
Senchuk Megan M.,
Van Raamsdonk Jeremy M.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201903235r
Subject(s) - stress (linguistics) , dynamics (music) , resistance (ecology) , microbiology and biotechnology , chemistry , biology , physics , ecology , philosophy , linguistics , acoustics
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.

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