SIRT5-mediated BCAT1 desuccinylation and stabilization leads to ferroptosis insensitivity and promotes cell proliferation in glioma.

ABSTRACT: Glioma is a highly aggressive brain tumor with limited treatment success due to its resistance to conventional therapies. Sirtuin 5 (SIRT5) has emerged as a promising target for cancer therapy, though it exhibits dual roles in different cancer types. In this study, we investigate the role of SIRT5 in glioma and its corresponding mechanisms. Our findings demonstrate that SIRT5 expression is elevated in glioma cells both in vitro and in vivo. SIRT5 knockdown significantly reduced glioma cell proliferation and enhanced sensitivity to ferroptosis. Proteomic and metabolomic analyses identifies branched-chain amino acid (BCAA) metabolism as a key downstream pathway regulated by SIRT5 through branched-chain aminotransferase 1 (BCAT1). Specifically, SIRT5-mediated desuccinylation of BCAT1 at K39 i

SUBMITTER: Wang T 

PROVIDER: S-EPMC11977203 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature