RT Journal Article
SR Electronic
T1 Activation of mitochondrial unfolded protein response protects against multiple exogenous stressors
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202101182
DO 10.26508/lsa.202101182
VO 4
IS 12
A1 Soo, Sonja K
A1 Traa, Annika
A1 Rudich, Paige D
A1 Mistry, Meeta
A1 Van Raamsdonk, Jeremy M
YR 2021
UL http://www.life-science-alliance.org/content/4/12/e202101182.abstract
AB The mitochondrial unfolded protein response (mitoUPR) is an evolutionarily conserved pathway that responds to mitochondria insults through transcriptional changes, mediated by the transcription factor ATFS-1/ATF-5, which acts to restore mitochondrial homeostasis. In this work, we characterized the role of ATFS-1 in responding to organismal stress. We found that activation of ATFS-1 is sufficient to cause up-regulation of genes involved in multiple stress response pathways including the DAF-16–mediated stress response pathway, the cytosolic unfolded protein response, the endoplasmic reticulum unfolded protein response, the SKN-1–mediated oxidative stress response pathway, the HIF-1-mediated hypoxia response pathway, the p38-mediated innate immune response pathway, and antioxidant genes. Constitutive activation of ATFS-1 increases resistance to multiple acute exogenous stressors, whereas disruption of atfs-1 decreases stress resistance. Although ATFS-1–dependent genes are up-regulated in multiple long-lived mutants, constitutive activation of ATFS-1 decreases lifespan in wild-type animals. Overall, our work demonstrates that ATFS-1 serves a vital role in organismal survival of acute stressors through its ability to activate multiple stress response pathways but that chronic ATFS-1 activation is detrimental for longevity.