SIRT5 inhibition impairs mitochondrial metabolism and enhances venetoclax-induced elimination of acute myeloid leukemia cells.

ABSTRACT: Metabolic reprogramming is a key focus of targeted therapies in acute myeloid leukemia (AML). The mitochondrial sirtuin SIRT5 removes succinyl groups from specific lysines and impacts cell metabolism, but its role in AML tumorigenesis has not been extensively explored. A recent study highlighted that SIRT5 regulates AML cell activity by modulating glutamine metabolism, but its molecular targets in AML remain unclear. This study aims to identify the substrates of SIRT5 in AML. It was found that a total of 83 proteins with 121 lysine (K) residues showed increased succinylation after SIRT5 knockdown, as determined by succinylome analysis of MOLM-13 cells. SIRT5 was validated to interact with HADHA, a key molecule in the fatty acid oxidation pathway. Knockdown of SIRT5 resulted in hypersucciny

SUBMITTER: Wang M 

PROVIDER: S-EPMC12310510 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature