SIRT1 inhibits mitochondrial hyperfusion associated mito-bulb formation to sensitize oral cancer cells for apoptosis in a mtROS-dependent signalling pathway.

ABSTRACT: SIRT1 (NAD-dependent protein deacetylase sirtuin-1), a class III histone deacetylase acting as a tumor suppressor gene, is downregulated in oral cancer cells. Non-apoptotic doses of cisplatin (CDDP) downregulate SIRT1 expression advocating the mechanism of drug resistance. SIRT1 downregulation orchestrates inhibition of DNM1L-mediated mitochondrial fission, subsequently leading to the formation of hyperfused mitochondrial networks. The hyperfused mitochondrial networks preserve the release of cytochrome C (CYCS) by stabilizing the mitochondrial inner membrane cristae (formation of mitochondrial nucleoid clustering mimicking mito-bulb like structures) and reducing the generation of mitochondrial superoxide to inhibit apoptosis. Overexpression of SIRT1 reverses the mitochondrial hyperfusion

SUBMITTER: Patra S 

PROVIDER: S-EPMC10638388 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature