1,25D3 reprograms mitochondrial quality control via sirtuin and sensitizes glioblastoma to chemotherapy - PubMed
4 days ago
- #chemotherapy
- #mitophagy
- #glioblastoma
- 1,25D3 reduces glioblastoma resistance to temozolomide by causing mitophagic overload and mitochondrial dysfunction.
- Mitochondrial sirtuin SIRT4 is identified as a key effector in mitochondrial metabolism and quality control triggered by 1,25D3.
- 1,25D3 activates mitophagy by upregulating SIRT4 through vitamin D receptor (VDR) signaling.
- SIRT4 suppresses glioblastoma glutamine metabolism by inhibiting glutamate dehydrogenase, limiting α-ketoglutarate availability.
- The VDR-SIRT4 axis shifts mitophagy from protective to lethal, sensitizing tumor cells while sparing normal tissue.
- 1,25D3 enhances chemotherapeutic efficacy by targeting mitochondrial quality control, offering a potential treatment for resistant glioblastoma.