Mapping the GDF15 Arm of the Integrated Stress Response in Human Cells and Tissues.

ABSTRACT: Mitochondrial stress activates the integrated stress response (ISR) and triggers cell-cell communication through the secretion of the metabokine growth differentiation factor 15 (GDF15). However, the gene network underlying the ISR remains poorly defined, particularly across metabolically diverse cellular states and tissues. Using RNAseq data from fibroblasts subjected to eleven metabolic perturbations, including genetic and pharmacological mitochondrial OxPhos defects, we showed that the ISR has multiple arms and developed an ISR ^GDF15 index quantifying the GDF15 arm of ISR activation in human cells. The ISR ^GDF15 index was validated using optogenetic activation of the ISR protein kinase R (PKR) in a stable cell line, demonstrating its rap

SUBMITTER: Smith JLM 

PROVIDER: S-EPMC11838536 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature