Abstract
Coordinated regulation of stress response pathways is crucial for cellular homeostasis. However, crosstalk between the different stress pathways and the physiological significance of this crosstalk remain poorly understood. In this study, using the model organism C. elegans, we discovered that suppression of the transcription factor LET-607/CREBH, a regulator of cellular defense and proteostatic responses, triggers adaptive induction of DAF-16-dependent stress responses. Suppression of LET-607 improves stress resistance and extends C. elegans lifespan in a DAF-16-dependent manner. We identified the sphingomyelin synthase SMS-5 to be a central mediator in the communication between LET-607 and DAF-16. SMS-5 reduces the contents of unsaturated phosphatidylcholine (PC), which activates DAF-16 through ITR-1-dependent calcium signaling and calcium-sensitive kinase PKC-2. Our data reveal the significance of crosstalk between different stress pathways in animal fitness and identify LET-607/CREBH and specific PC as regulators of DAF-16 and longevity.
Highlights
In order to defend against environmental and cellular stresses, animals have evolved complex stress response pathways
It is widely hypothesized that interruption of one key stress response pathway could compromise overall cellular function and survival
Suppression of LET-607, a regulator of defense and proteostatic responses, was shown to adaptively activate DAF-16, which is a crucial regulator of general stress responses
Summary
In order to defend against environmental and cellular stresses, animals have evolved complex stress response pathways. Disturbance of these pathways leads to compromised cellular homeostasis and aging [1]. Stress responses typically activate in different parts of the cell, which are controlled by core transcription factors. These transcription factors each regulate a specific subset of genes that enable the cell to cope with compartment-specific stresses. Disturbing one stress pathway may induce adaptive stress responses in other parts of the cell This hypothesis has been corroborated by recent research investigating the communication between mitochondrial and cytosolic proteostatic response pathways. Other than research into proteostatic pathways, little is known about whether and how stress pathways communicate to enable overall cellular homeostasis and animal fitness
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
