Multi-omics analysis identifies ATF4 as a key regulator of the mitochondrial stress response in mammals

DSpace/Manakin Repository

Multi-omics analysis identifies ATF4 as a key regulator of the mitochondrial stress response in mammals

Citable link to this page

 

 
Title: Multi-omics analysis identifies ATF4 as a key regulator of the mitochondrial stress response in mammals
Author: Quirós, Pedro M.; Prado, Miguel A.; Zamboni, Nicola; D’Amico, Davide; Williams, Robert W.; Finley, Daniel; Gygi, Steven P.; Auwerx, Johan

Note: Order does not necessarily reflect citation order of authors.

Citation: Quirós, Pedro M., Miguel A. Prado, Nicola Zamboni, Davide D’Amico, Robert W. Williams, Daniel Finley, Steven P. Gygi, and Johan Auwerx. 2017. “Multi-omics analysis identifies ATF4 as a key regulator of the mitochondrial stress response in mammals.” The Journal of Cell Biology 216 (7): 2027-2045. doi:10.1083/jcb.201702058. http://dx.doi.org/10.1083/jcb.201702058.
Full Text & Related Files:
Abstract: Mitochondrial stress activates a mitonuclear response to safeguard and repair mitochondrial function and to adapt cellular metabolism to stress. Using a multiomics approach in mammalian cells treated with four types of mitochondrial stressors, we identify activating transcription factor 4 (ATF4) as the main regulator of the stress response. Surprisingly, canonical mitochondrial unfolded protein response genes mediated by ATF5 are not activated. Instead, ATF4 activates the expression of cytoprotective genes, which reprogram cellular metabolism through activation of the integrated stress response (ISR). Mitochondrial stress promotes a local proteostatic response by reducing mitochondrial ribosomal proteins, inhibiting mitochondrial translation, and coupling the activation of the ISR with the attenuation of mitochondrial function. Through a trans–expression quantitative trait locus analysis, we provide genetic evidence supporting a role for Fh1 in the control of Atf4 expression in mammals. Using gene expression data from mice and humans with mitochondrial diseases, we show that the ATF4 pathway is activated in vivo upon mitochondrial stress. Our data illustrate the value of a multiomics approach to characterize complex cellular networks and provide a versatile resource to identify new regulators of mitochondrial-related diseases.
Published Version: doi:10.1083/jcb.201702058
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496626/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:34868852
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters