SIRT6 Regulates Protein Synthesis and Folding Through Nucleolar Remodeling - PubMed
5 days ago
- #SIRT6
- #proteostasis
- #neurodegeneration
- SIRT6 plays a critical role in maintaining proteostasis, which is often lost during aging and neurodegeneration.
- SIRT6 negatively regulates global translation by controlling ribosomal genes, nucleolar function, and TIP5 chromatin localization.
- Deletion of SIRT6 increases nucleolar size, rRNA production, and protein translation, but fails to upregulate chaperones, leading to protein aggregation.
- A C. elegans model (sir-2.4 KO) shows reduced heat shock resistance and accelerated age-dependent motility loss, indicating proteostasis-stress intolerance.
- SIRT6 deficiency leads to proteostasis loss through nucleolar dysfunction, highlighting chromatin dysregulation as a starting point for neurodegeneration.
- Pharmacologically reducing protein translation rates can rescue the effects of SIRT6 deficiency.