Figure 7 from Translational Activation of ATF4 through Mitochondrial Anaplerotic Metabolic Pathways Is Required for DLBCL Growth and Survival
<p>Graphical summary of SIRT3–ATF4 regulation in DLBCLs. Left, DLBCL cells depend on glutamine anaplerosis driven by SIRT3 and GDH to produce metabolic precursors from the TCA cycle for cell survival and proliferation, which also suppress autophagy and the downstream protein recycling in the l...
Saved in:
| Main Author: | |
|---|---|
| Other Authors: | , , , , , , , , , , |
| Published: |
2025
|
| Subjects: | |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | <p>Graphical summary of SIRT3–ATF4 regulation in DLBCLs. Left, DLBCL cells depend on glutamine anaplerosis driven by SIRT3 and GDH to produce metabolic precursors from the TCA cycle for cell survival and proliferation, which also suppress autophagy and the downstream protein recycling in the lysosome. The active proliferation and high metabolic demand of DLBCL cells leads to a shortage of NEAAs and results in translational activation of ATF4, which can transcribe target genes for importation of extracellular nutrients to maintain the amino acid flux. Right, pharmaceutically inhibiting or knocking down SIRT3 suppresses the TCA cycle metabolism as a metabolic engine and decreases the consumption of amino acids (including NEAAs). The reduced TCA cycle metabolism in turn triggers activation of autophagy, which produces amino acids from lysosomal protein degradations to compensate the metabolic suppression. However, the increased amino acids cannot be used in the mitochondria of the defective TCA cycle, but instead block the translation of ATF4 and then shut down the nutrient importation. Together, these induce metabolic stress in DLBCL cells and lead to cell-cycle arrest and death. The larger, bold font indicates more activity or function of indicated proteins or biological activities. The thickness of lines and numbers of arrows indicate the impacts of upstream molecules/biological activities to downstream targets.</p> |
|---|