PT  - JOURNAL ARTICLE
AU  - Soo, Sonja K
AU  - Traa, Annika
AU  - Rudich, Paige D
AU  - Mistry, Meeta
AU  - Van Raamsdonk, Jeremy M
TI  - Activation of mitochondrial unfolded protein response protects against multiple exogenous stressors
AID  - 10.26508/lsa.202101182
DP  - 2021 Dec 01
TA  - Life Science Alliance
PG  - e202101182
VI  - 4
IP  - 12
4099  - http://www.life-science-alliance.org/content/4/12/e202101182.short
4100  - http://www.life-science-alliance.org/content/4/12/e202101182.full
SO  - Life Sci. Alliance2021 Dec 01; 4
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.